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1.
Molecules ; 26(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443422

RESUMO

A significant increase in the production of plastic materials and the expansion of their areas of application contributed to the accumulation of a large amount of waste of polymeric materials. Most of the polymer composition is made up of plasticizers. Phthalate plasticizers have been recognized as potentially hazardous to humans and the environment due to the long period of their biodegradation and the formation of persistent toxic metabolites. It is known that the industrial plasticizer dioctyl adipate is characterized by reduced toxicity and a short biodegradation period. The paper describes the synthesis of a number of new asymmetric esters based on adipic acid and ethoxylated butanol by azeotropic esterification. The receipt of the products was confirmed by IR spectra. The physicochemical properties of the synthesized compounds were investigated. The glass transition temperatures of PVC composites plasticized with alkyl butoxyethyl adipates were determined using DSC analysis. The ecological safety of esters was assessed by the phytotesting method. Samples of adipates were tested for fungal resistance, and the process of their biodegradation in soil was also studied. It is shown that the synthesized esters have good plasticizing properties and are environmentally safe. When utilized under natural conditions, they can serve as a potential source of carbon for soil microorganisms and do not form stable toxic metabolites; therefore, they are not able to accumulate in nature; when the plasticizers under study are disposed of in the soil, toxic substances do not enter.


Assuntos
Adipatos/toxicidade , Ecotoxicologia , Etanol/química , Plastificantes/toxicidade , Adipatos/síntese química , Adipatos/química , Biodegradação Ambiental , Varredura Diferencial de Calorimetria , Etanol/síntese química , Fungos/efeitos dos fármacos , Vidro/química , Lepidium/efeitos dos fármacos , Cloreto de Polivinila/química , Raphanus/efeitos dos fármacos , Solo , Espectrofotometria Infravermelho , Temperatura de Transição
2.
Environ Toxicol Pharmacol ; 87: 103726, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34418532

RESUMO

Epidemiological and experimental studies have shown that di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, can aggravate allergic diseases. DEHP promotes adaptive immune responses, although its effect on the innate immune system remains largely unknown. The present study investigated the effects of DEHP on group 2 innate lymphoid cells (ILC2) that produce Th2 cytokines in response to epithelial cell-derived cytokines, such as interleukin (IL)-33. ILC2 (lineage-negative, CD45.2+, Sca1+, KLRG1+) were isolated from the lungs of C57BL/6 J mice. Co-exposure to DEHP and IL-33 significantly increased IL-5 release from ILC2, whose level was higher than that of the vehicle and IL-33 alone. The effects of DEHP in the presence of IL-33 showed an inverted-U dose-response. The present is the first report showing that DEHP exacerbates allergy through the innate immune system.


Assuntos
Citocinas/imunologia , Dietilexilftalato/toxicidade , Imunidade Inata/efeitos dos fármacos , Interleucina-33/farmacologia , Linfócitos/efeitos dos fármacos , Plastificantes/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Hipersensibilidade/imunologia , Interleucina-5/imunologia , Pulmão/citologia , Pulmão/imunologia , Linfócitos/imunologia , Masculino , Camundongos Endogâmicos C57BL
3.
J Hazard Mater ; 419: 126426, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34166954

RESUMO

The invertebrate innate immunity is a crucial characteristic that represents a valuable basis for studying common biological responses to environmental pollutants. Cell defence mechanisms are key players in protecting the organism from infections and foreign materials. Many haemocyte-associated immunological parameters have been reported to be immunologically sensitive to aquatic toxins (natural or artificial). Environmental plastic pollution poses a global threat to ecosystems and human health due to plastic vast and extensive use as additives in various consumer products. In recent years, studies have been done to evaluate the effects of plasticizers on humans and the environment, and their transmission and presence in water, air, and indoor dust, and so forth. Hence, the development of biomarkers that evaluate biological responses to different pollutants are essential to obtain important information on plasticizers' sublethal effects. This review analyses the current advances in the adverse effects of plasticizers (as emerging contaminants), such as immunological response disruption. The review also shows a critical analysis of the effects of the most widely used plasticizers on haemocytes. The advantages of an integrative approach that uses chemical, genetic, and immunomarker assays to monitor toxicity are highlighted. All these factors are imperative to ponder when designing toxicity studies to recognize the potential effects of plasticizers like bisphenol A and phthalates.


Assuntos
Ácidos Ftálicos , Plastificantes , Animais , Compostos Benzidrílicos , Ecossistema , Genômica , Humanos , Imunidade , Invertebrados , Fenóis , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade
4.
Ecotoxicol Environ Saf ; 221: 112418, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34146982

RESUMO

BACKGROUND: Bisphenol A (BPA), a widely used plastic monomer and plasticizer, is detectable in blood, urine and semen of a healthy people, with concentrations ranging from 0.1 nM to 10 nM. It has been shown that in vitro exposure of BPA as low as 0.001 nM could significantly inhibited mouse sperm motility and acrosome reaction. However, it is still unclear whether BPA at those physiologically detectable concentration affects human sperm. METHODS: The effects of different concentrations of BPA (0, 10-3, 10-2, 10-1, 10, 103 nM) on sperm functions were examined, including human sperm viability, kinematic parameters, hyperactivation and capacitation. RESULTS: BPA caused a remarkable decline in human sperm viability, motility and progressive motility, hyperactivation, capacitation and progesterone-induced acrosome reaction. Mechanism studies showed that BPA could suppress the protein tyrosine phosphorylation level of human sperm, but had no effect on sperm calcium signaling. CONCLUSIONS: Physiologically detectable concentrations of BPA may impair human sperm functions via suppressing protein tyrosine phosphorylation of human sperm, implying that environmental pollution of BPA might be a factor contributing to male infertility.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Plastificantes/toxicidade , Espermatozoides/efeitos dos fármacos , Reação Acrossômica/efeitos dos fármacos , Humanos , Masculino , Fosforilação/efeitos dos fármacos , Progesterona/metabolismo , Proteínas/metabolismo , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/fisiologia , Tirosina/metabolismo
5.
Sci Total Environ ; 786: 147371, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-33965815

RESUMO

Phthalate esters (PAEs) are one of the most widely used plasticizers in polymer products and humans are increasingly exposed to them. The constant exposure to PAEs-contained products has raised some concerns against human health. Thus, the impacts of PAEs and their metabolites on human health require a comprehensive study for a better understanding of the associated risks. Here, we attempt to review eight main health effects of PAE exposure according to the most up-to-date studies. We found that epidemiological studies demonstrated a consistent association between PAE exposure (especially DEHP and its metabolites) and a decrease in sperm quality in males and symptom development of ADHD in children. Overall, we found insufficient evidence and lack of consistency of the association between PAE exposure and cardiovascular diseases (hypertension, atherosclerosis, and CHD), thyroid diseases, respiratory diseases, diabetes, obesity, kidney diseases, intelligence performance in children, and other reproductive system-related diseases (anogenital distance, girl precocious puberty, and endometriosis). Future studies (longitudinal and follow-up investigations) need to thoroughly perform in large-scale populations to yield more consistent and powerful results and increase the precision of the association as well as enhance the overall understanding of potential human health risks of PAEs in long-term exposure.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Criança , China , Dibutilftalato , Ésteres , Feminino , Humanos , Masculino , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade
6.
Artigo em Inglês | MEDLINE | ID: mdl-33925988

RESUMO

BACKGROUND: The general population (including children) is exposed to chemical mixtures. Plasticizers such as Bisphenol A (BPA) and Phthalates (mainly Bis(2-ethylhexyl) phthalate-DEHP) are widespread contaminants classified as endocrine disrupters which share some toxicological profiles and coexist in food and environment. METHODS: To identify hazards of DEHP and BPA mixtures, the juvenile toxicity test-where rodents are in peripubertal phase of development, resembling childhood-was selected using exposure data from biomonitoring study in children. Biological activity and potential enhanced and/or reduced toxicological effects of mixtures due to common mechanisms were studied, considering endpoints of metabolic, endocrine and reproductive systems. The degree of synergy or antagonism was evaluated by synergy score calculation, using present data and results from the single compound individually administered. RESULTS: In metabolic system, synergic interaction predominates in female and additive in male rats; in the reproductive and endocrine systems, the co-exposure of BPA and DEHP showed interactions mainly of antagonism type. CONCLUSIONS: The present approach allows to evaluate, for all the endpoints considered, the type of interaction between contaminants relevant for human health. Although the mode of action and biological activities of the mixtures are not completely addressed, it can be of paramount usefulness to support a more reliable risk assessment.


Assuntos
Dietilexilftalato , Disruptores Endócrinos , Animais , Compostos Benzidrílicos/toxicidade , Criança , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Masculino , Fenóis/toxicidade , Ácidos Ftálicos , Plastificantes/toxicidade , Ratos
7.
Artigo em Inglês | MEDLINE | ID: mdl-33807420

RESUMO

Endometriosis is an inflammatory and estrogen-dependent gynecological disease associated with exposure to environmental endocrine disruptors. n-Butyl benzyl phthalate (BBP), a ubiquitous plasticizer, has weak estrogenic activity, and exposure to BBP is associated with endometriosis. We aimed to elucidate the immunomodulatory effect of BBP on endometriosis development. We previously established a surgery-induced endometriosis-like murine model. In the present study, we exposed those mice to BBP 10 days prior to surgery and 4 weeks after surgery at physiologically relevant doses to mimic human exposure. Chronic exposure to BBP did not promote the growth of endometriotic lesions; however, the lesion survival rate in BBP-treated mice did increase significantly compared with control mice. Multiparametric flow cytometry showed that BBP exposure did not affect the homeostasis of infiltrated immune subsets in lesions but did enhance CD44 (adhesion marker) expression on plasmacytoid dendritic cells (pDCs). Blocking CD44 interactions locally inhibited endometriotic lesion growth. Immunofluorescence results further confirmed that CD44 blocking inhibited pDC infiltration and reduced the frequency of CD44+ pDCs in endometriotic tissues. BBP also disrupted the estrus cycle in these mice. This study suggests that chronic exposure to low-dose BBP may promote survival of endometriotic tissue through CD44-expressing pDCs.


Assuntos
Disruptores Endócrinos , Endometriose , Ácidos Ftálicos , Animais , Feminino , Humanos , Camundongos , Plastificantes/toxicidade
8.
Toxicol Appl Pharmacol ; 419: 115514, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33798595

RESUMO

Phthalates as plasticizers are widely used in many consumer products. Dipentyl phthalate (DPeP) is one of phthalates. However, there are currently few data on whether DPeP exposure affects rat Leydig cell development. In this study, we investigated the effects of in utero DPeP exposure on Leydig cell development in the testes of male newborn and adult rats. From gestational days 14 to 21, Sprague-Dawley pregnant rats were gavaged vehicle (corn oil, control) or DPeP (10, 50, 100, and 500 mg/kg body weight/day). Testosterone and the expression of Leydig cell genes and proteins in the testis at birth and at postnatal day 56 were examined. DPeP dose-dependently reduced serum testosterone levels of male offspring at birth and at postnatal day 56 at 100 and 500 mg/kg and lowered serum luteinizing hormone levels at adult males at ≥10 mg/kg when compared with the control. In addition, DPeP increased number of fetal Leydig cells by inducing their proliferation but down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Insl3 in fetal Leydig cells per se. DPeP reduced number of adult Leydig cells by inducing cell apoptosis and down-regulated the expression of Lhcgr and Star in adult Leydig cells at postnatal day 56. DPeP lowered SIRT1 and BCL2 levels in the testis of adult rats. In conclusion, DPeP adversely affects both fetal and adult Leydig cell development after in utero exposure.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Testículo/efeitos dos fármacos , Fatores Etários , Animais , Apoptose/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Idade Gestacional , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Hormônio Luteinizante/sangue , Masculino , Exposição Materna , Gravidez , Ratos Sprague-Dawley , Testículo/embriologia , Testículo/metabolismo , Testosterona/sangue
9.
Int J Mol Sci ; 22(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920546

RESUMO

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8-12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior.


Assuntos
Dibutilftalato/toxicidade , Dietilestilbestrol/toxicidade , Estrogênios não Esteroides/farmacologia , Hipotálamo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Comportamento Sexual Animal , Animais , Aromatase/genética , Aromatase/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Ocitocina/genética , Ocitocina/metabolismo , Plastificantes/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Transcriptoma , Vasopressinas/genética , Vasopressinas/metabolismo
10.
Int J Mol Sci ; 22(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923623

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system.


Assuntos
Metilação de DNA , Dietilexilftalato/toxicidade , Epigênese Genética , Plastificantes/toxicidade , Efeitos Tardios da Exposição Pré-Natal/genética , Espermatozoides/efeitos dos fármacos , Animais , Peso Corporal , Feminino , Genitália Masculina/anatomia & histologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley
11.
Int J Biol Macromol ; 181: 1092-1103, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33892039

RESUMO

This study explores the effect of plasticisers (lotader AX8900, polyethylene glycol and triethyl citrate) on biodegradability of polylactic acid (PLA) and its composites with halloysite nanotubes and ramie fabric by soil burial method. Changes in surface morphology and mechanical properties were evaluated to quantify the degradation behaviour of all samples. The results showed that the relative loss in tensile strength of ramie-PLA composites was more than that of neat PLA or plasticised PLA films. Also, ramie-PLA composite, where ramie fabric was treated with diammonium orthophosphate, had degraded entirely after 60 days of soil burial. It was also confirmed by Fourier transform infrared spectroscopy that the chemical structures of neat PLA and plasticised PLA films changed after the soil burial test. The use of these additives not only reduces the brittleness of PLA but also accelerates the biodegradation rate of PLA. Thus, PLA, along with additives, can help in reduction of carbon footprint and other environmental issues customarily associated with petro based polymers. Therefore, the finding supports the notion of PLA usage as a viable alternative to fossil fuel-based materials.


Assuntos
Biodegradação Ambiental , Boehmeria/química , Nanotubos/química , Solo/química , Citratos/química , Ácido Láctico/química , Plastificantes/química , Plastificantes/toxicidade , Poliésteres/química , Polietilenoglicóis/química , Polímeros/química , Resistência à Tração/efeitos dos fármacos , Água/química
12.
Theranostics ; 11(10): 4992-5009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754040

RESUMO

Rationale: Accumulated evidence indicates that environmental plasticizers are a threat to human and animal fertility. Di (2-ethylhexyl) phthalate (DEHP), a plasticizer to which humans are exposed daily, can trigger reproductive toxicity by acting as an endocrine-disrupting chemical. In mammals, the female primordial follicle pool forms the lifetime available ovarian reserve, which does not undergo regeneration once it is established during the fetal and neonatal period. It is therefore critical to examine the toxicity of DEHP regarding the establishment of the ovarian reserve as it has not been well investigated. Methods: The ovarian cells of postnatal pups, following maternal DEHP exposure, were prepared for single cell-RNA sequencing, and the effects of DEHP on primordial follicle formation were revealed using gene differential expression analysis and single-cell developmental trajectory. In addition, further biochemical experiments, including immunohistochemical staining, apoptosis detection, and Western blotting, were performed to verify the dataset results. Results: Using single-cell RNA sequencing, we revealed the gene expression dynamics of female germ cells and granulosa cells following exposure to DEHP in mice. Regarding germ cells: DEHP impeded the progression of follicle assembly and interfered with their developmental status, while key genes such as Lhx8, Figla, and others, strongly evidenced the reduction. As for granulosa cells: DEHP likely inhibited their proliferative activity, and activated the regulation of cell death. Furthermore, the interaction between ovarian cells mediated by transforming growth factor-beta signaling, was disrupted by DEHP exposure, since the expression of GDF9, BMPR1A, and SMAD3 was affected. In addition, DNA damage and apoptosis were elevated in germ cells and/or somatic cells. Conclusion: These findings offer substantial novel insights into the reproductive toxicity of DEHP exposure during murine germ cell cyst breakdown and primordial follicle formation. These results may enhance the understanding of DEHP exposure on reproductive health.


Assuntos
Dietilexilftalato/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Plastificantes/toxicidade , Animais , Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/efeitos dos fármacos , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Células da Granulosa/metabolismo , Fator 9 de Diferenciação de Crescimento/efeitos dos fármacos , Fator 9 de Diferenciação de Crescimento/genética , Proteínas com Homeodomínio LIM/efeitos dos fármacos , Proteínas com Homeodomínio LIM/genética , Camundongos , Folículo Ovariano/citologia , Folículo Ovariano/embriologia , Folículo Ovariano/metabolismo , Óvulo/metabolismo , RNA-Seq , Análise de Célula Única , Proteína Smad3/efeitos dos fármacos , Proteína Smad3/genética , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genética
13.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33649816

RESUMO

Di (2­ethylhexyl) phthalate (DEHP), an environmental pollutant, is widely used as a plasticizer and causes serious pollution in the ecological environment. As previously reported, exposure to DEHP may cause thyroid dysfunction of the hypothalamic­pituitary­thyroid (HPT) axis. However, the underlying role of DEHP remains to be elucidated. The present study performed intragastrical administration of DEHP (150, 300 and 600 mg/kg) once a day for 90 consecutive days. DEHP­stimulated oxidative stress increased the thyroid follicular cavity diameter and caused thyrocyte oedema. Furthermore, DEHP exposure altered mRNA and protein levels. Thus, DEHP may perturb TH homeostasis by affecting biosynthesis, biotransformation, bio­transportation, receptor levels and metabolism through disruption of the HPT axis and activation of the thyroid­stimulating hormone (TSH)/TSH receptor signaling pathway. These results identified the formerly unappreciated endocrine­disrupting activities of phthalates and the molecular mechanisms of DEHP­induced thyrotoxicity.


Assuntos
Dietilexilftalato/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Plastificantes/toxicidade , Ratos Wistar , Receptores da Tireotropina/genética , Receptores da Tireotropina/metabolismo , Receptores do Hormônio Liberador da Tireotropina/genética , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Glândula Tireoide/crescimento & desenvolvimento , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Hormônios Tireóideos/metabolismo , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/metabolismo , Tireotropina Subunidade beta/genética , Tireotropina Subunidade beta/metabolismo
14.
Int J Med Sci ; 18(5): 1247-1258, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33526986

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) that is one of the most commonly used phthalates in manufacturing plastic wares regulates tumorigenesis. Thymosin beta-4 (TB4), an actin-sequestering protein, has been reported as a novel regulator to form primary cilia that are antenna-like organelles playing a role in various physiological homeostasis and pathological development including tumorigenesis. Here, we investigated whether DEHP affects tumor growth via primary cilium (PC) formation via the axis of TB4 gene expression and the production of reactive oxygen species (ROS). Tumor growth was increased by DEHP treatment that enhanced TB4 expression, PC formation and ROS production. The number of cells with primary cilia was enhanced time-dependently higher in HeLa cells incubated in the culture medium with 0.1% fetal bovine serum (FBS). The number of cells with primary cilia was decreased by the inhibition of TB4 expression. The incubation of cells with 0.1% FBS enhanced ROS production and the transcriptional activity of TB4 that was reduced by ciliobrevin A (CilioA), the inhibitor of ciliogenesis. ROS production was decreased by catalase treatment but not by mito-TEMPO, which affected to PC formation with the same trend. H2O2 production was reduced by siRNA-based inhibition of TB4 expression. H2O2 also increased the number of ciliated cells, which was reduced by siRNA-TB4 or the co-incubation with CilioA. Tumor cell viability was maintained by ciliogenesis, which was correlated with the changes of intracellular ATP amount rather than a simple mitochondrial enzyme activity. TB4 overexpression enhanced PC formation and DEHP-induced tumor growth. Taken together, data demonstrate that DEHP-induced tumor growth might be controlled by PC formation via TB4-H2O2 axis. Therefore, it suggests that TB4 could be a novel bio-marker to expect the risk of DEHP on tumor growth.


Assuntos
Dietilexilftalato/toxicidade , Peróxido de Hidrogênio/metabolismo , Melanoma Experimental/patologia , Plastificantes/toxicidade , Neoplasias Cutâneas/patologia , Timosina/metabolismo , Animais , Carcinogênese/induzido quimicamente , Carcinogênese/patologia , Sobrevivência Celular/efeitos dos fármacos , Cílios/efeitos dos fármacos , Cílios/metabolismo , Dietilexilftalato/administração & dosagem , Células HEK293 , Células HeLa , Humanos , Injeções Intraperitoneais , Masculino , Melanoma Experimental/induzido quimicamente , Camundongos , Plastificantes/administração & dosagem , Neoplasias Cutâneas/induzido quimicamente
15.
Artigo em Inglês | MEDLINE | ID: mdl-33563085

RESUMO

The objective of this study was to investigate 13 phthalic acid esters (PAEs) with medium or long straight-alkyl-chain, branching or unsaturated side chains, because their structural characteristics make them difficult to biodegrade or highly toxic. A biodegradability and biotoxicity multi-effect pharmacophore model was built using comprehensive evaluation method. The results suggested that introducing hydrophobic groups to the side chains of the PAEs could improve the molecules' biodegradability and biotoxicity effects simultaneously. Thus, 40 target PAE (HEHP, DNOP, DUP) derivatives were designed. Two environmentally friendly PAE derivatives (HEHP-Anthryl and HEHP-Naphthyl) were screened via the test of environmental friendliness and functionality. In addition, the biodegradation and biotoxicity of derivatives were found to have improved as a result of the change in van der Waals forces between molecules and their corresponding proteins. Moreover, the environmental safety of the screened PAE derivatives was confirmed by predicting the toxicity of their intermediates and calculating the energy barrier values for biodegradation and metabolic pathways. This study could provide theoretical guidance for the practical development of environmentally friendly plasticizer.


Assuntos
Ésteres , Modelos Teóricos , Ácidos Ftálicos , Plastificantes , Animais , Biodegradação Ambiental , Decápodes/efeitos dos fármacos , Ésteres/química , Ésteres/metabolismo , Ésteres/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/toxicidade , Plastificantes/química , Plastificantes/metabolismo , Plastificantes/toxicidade
16.
Sci Total Environ ; 771: 145418, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33548714

RESUMO

Phthalates (PAEs) are of wide concern because they are commonly used in various plastic products as plasticizers, and can found their way into the environment. However, their interaction with the environment and their toxicity in aquatic animals is still a matter of intense debate. In this review on PAEs in aquatic environments (lakes, rivers and seas), it is found that there is a large variety and abundance of PAEs in developing countries, and the total concentration of PAEs even exceeds 200 µg / L. The interaction between metabolic processes involved in the toxicity induced by various PAEs is summarized for the first time in the article. Exposure of PAEs can lead to activation of the detoxification system CYP450 and endocrine system receptors of aquatic animals, which in turn causes oxidative stress, metabolic disorders, endocrine disorders, and immunosuppression. Meanwhile, each system can activate / inhibit each other, causing genotoxicity and cell apoptosis, resulting in the growth and development of organisms being blocked. The mixed PAEs shows no cumulative toxicity changes to aquatic animals. For the combined pollution of other chemicals and PAEs, PAE can act as an agonist or antagonist, leading to combined toxicity in different directions. Phthalate monoesters (MPEs), the metabolites of PAEs, are also toxic to aquatic animals, however, the toxicity is weaker than the corresponding parent compounds. This review summarizes and analyzes the current ecotoxicological effects of PAEs on aquatic animals, and provides guidance for future research.


Assuntos
Ácidos Ftálicos , Animais , China , Ésteres , Lagos , Ácidos Ftálicos/toxicidade , Plastificantes/análise , Plastificantes/toxicidade , Rios
17.
Artigo em Inglês | MEDLINE | ID: mdl-33412299

RESUMO

Diisononyl phthalate (DINP) as one of the most commonly used phthalates, has been found in various environmental samples and is considered to have potential risks to ecosystem. Till now, DINP has no clear effect consensus on insects from development to behavior and even mechanisms. Here, Drosophila melanogaster was selected as model organisms and the toxic effects of DINP (0.1%, 0.2%, 0.5% and 1.0%) (v/v) on its metamorphosis, crawling behavior, intestinal cells and cellular redox balance were investigated. During metamorphosis process, lower hatching rate, longer development time, lighter body weight and malformation were observed at high concentration groups. The crawling ability of larvae was severely inhibited by DINP and the movement distance was drastically reduced. DINP could cause severe damage to the larval intestinal cells in the dose-dependent and time-dependent manners. DINP was found to induce redox imbalance with activities of two important antioxidant enzymes (catalase (CAT) and superoxide dismutase (SOD)) increasing, and reactive oxygen species (ROS) level fluctuation in larvae. Our findings provide theoretical basis and data support for scientific management of DINP to reduce ecological risk.


Assuntos
Drosophila melanogaster , Larva , Metamorfose Biológica/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Plastificantes/toxicidade , Animais , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento
18.
Int Immunopharmacol ; 91: 107323, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33385713

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which manifests itself in early childhood and is distinguished by recurring behavioral patterns, and dysfunction in social/communication skills. Ubiquitous environmental pollutant, di-2-ethylhexyl phthalate (DEHP) is one of the most frequently used plasticizers in various industrial products, e.g. vinyl flooring, plastic toys, and medical appliances. DEHP gets easily released into the environment and leads to human exposure through various routes. DEHP has been described to be linked with oxidative stress in various organs in animal/human studies. Increased concentration of DEHP has also been detected in ASD children which indicates an association between phthalates exposure and ASD. However, effect of DEHP on autism-like behavior has not been investigated previously. Therefore, this study probed the effect of DEHP on autism-like behavior (marble burying, self-grooming and sociability) and innate immune cells (dendritic cells/neutrophils)/cerebellar oxidant-antioxidant balance (NFkB, iNOS, NADPH oxidase, nitrotyrosine, lipid peroxides, Nrf2, SOD, GPx) in BTBR and C57 mice. Our data show that DEHP treatment causes worsening of autism-like behavior in BTBR mice which is associated with enhancement of oxidative stress in innate immune cells and cerebellum with concomitant lack of antioxidant protection. DEHP also causes oxidative stress in C57 mice in both innate immune cells and cerebellar compartment, however there is Nrf2-mediated induction of enzymatic antioxidants which protects them from upregulated oxidative stress. This proposes the notion that ubiquitous environmental pollutants such as DEHP may be involved in the pathogenesis/progression of ASD through dysregulation of antioxidant-antioxidant balance in innate immune cells and cerebellum.


Assuntos
Transtorno Autístico/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Dietilexilftalato/toxicidade , Poluentes Ambientais/toxicidade , Imunidade Inata/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Plastificantes/toxicidade , Animais , Antioxidantes/metabolismo , Transtorno Autístico/enzimologia , Transtorno Autístico/imunologia , Transtorno Autístico/psicologia , Cerebelo/enzimologia , Cerebelo/imunologia , Modelos Animais de Doenças , Asseio Animal/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Comportamento Social
19.
Ecotoxicol Environ Saf ; 208: 111746, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396072

RESUMO

Plasticizers are widespread environmental contaminants that have been described as obesogens in terrestrial vertebrates. However, its effects on fish lipids homeostasis are almost unknown. This work explores the use of PLHC-1 cells as an alternative model to assess the disruption of hepatic lipids by plastic additives and to gather information on the mode of action of these chemicals in fish. PLHC-1 lipid extracts were analyzed by flow injection coupled to high resolution mass spectrometry (FIA-ESI(+/-)-Orbitrap-Exactive) after 24 h exposure of the cells to the selected plasticizers: dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), bisphenol F (BPF), and chlorinated bisphenol A diglycidyl ether (BADGE·2HCl). The analysis of the culture medium and the intracellular concentration of the chemicals revealed the highest bioconcentration of BADGE·2HCl, DBP and DEHP, which was in agreement with the strongest alteration of the cells lipidome. BADGE·2HCl induced a significant depletion of triacylglycerides (TGs), while DEHP and DBP stimulated the accumulation of TGs. Exposure to BPF induced the generation of reactive oxygen species in PLHC-1 cells and a significant depletion of phosphatidylcholine (PC)- and phosphatidylethanolamine (PE)-plasmalogens, and TGs (cell depots of polyunsaturated fatty acids). Overall, this study evidences different modes of action of plastic additives in topminnow liver cells, describes differential lipidomic signatures, and highlights the higher lipotoxicity of BADGE·2HCl and BPF compared to BPA.


Assuntos
Plásticos/toxicidade , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Animais , Compostos Benzidrílicos , Dibutilftalato , Compostos de Epóxi , Fundulidae , Hepatócitos , Fígado/efeitos dos fármacos , Modelos Biológicos , Fenóis , Ácidos Ftálicos , Plastificantes/toxicidade
20.
Ecotoxicol Environ Saf ; 208: 111620, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396140

RESUMO

Di(2-ethylhexyl) adipate (DEHA) is a widely used plasticizer and prevalent environmental contaminant. In this study, DEHA concentrations in the milk, cheese, and butter samples wrapped with food-grade commercial polyethylene films and stored at 4 °C for 30 days were detected using gas chromatographic analysis. Also, the effects of exposure to a high dose of DEHA for a long duration on the liver, brain, and heart of Wistar rats were assessed. Besides, the possible beneficial effect of Peganum harmala oil (PGO), in relieving DEHA induced adverse effects was explored. For this purpose, four groups (8 rats/group) were orally given physiological saline, PGO (320 mg/kg bwt), DEHA (2000 mg/kg bwt), or PGO + DEHA for 60 days. The results revealed that the DEHA concentrations in the tested dairy products were ordered as follows: (butter > cheese > milk). Notably, the detected levels in butter were higher than the specific migration limit in foods. DEHA induced a significant increase in the serum levels of glucose, alanine transaminase, aspartate transaminase, acetylcholine esterase, creatine kinase-myocardium bound, malondialdehyde, tumor necrosis factor-α, and interleukin-1ß. But, significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, and hypocholesterolemia were evident following DEHA exposure. A significant reduction in the serum level of superoxide dismutase, reduced glutathione, and brain-derived neurotrophic factor was recorded. Besides, a significant downregulation in hepatic CYP2E1, brain glial fibrillary acidic protein, and cardiac troponin I gene expression was noticed. Moreover, DEHA exposure induced a significant decrease in Bcl-2 immunolabeling, but Caspase-3 immunoexpression was increased. On the contrary, PGO significantly recused DEHA injurious impacts. Therefore, PGO could represent a promising agent for preventing DEHA-induced hepatotoxicity, neurotoxicity, and cardiotoxicity.


Assuntos
Adipatos/toxicidade , Encéfalo/efeitos dos fármacos , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Peganum/química , Óleos Vegetais/farmacologia , Plastificantes/toxicidade , Adipatos/análise , Anemia/sangue , Anemia/prevenção & controle , Animais , Glicemia/análise , Encéfalo/metabolismo , Encéfalo/patologia , Laticínios/análise , Embalagem de Alimentos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Plastificantes/análise , Ratos , Ratos Wistar , Fatores de Tempo
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