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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.
Toxicol Lett ; 315: 64-76, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419470

RESUMO

To test the hypothesis that 3-7 ring polycyclic aromatic hydrocarbons (PAHs) are responsible for the prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS), the present study evaluates the PDT potency of DMSO-extracts of 7 heavy fuel oils (HFO), varying in their PAH content, and 1 highly refined base oil (HRBO), containing no aromatics, in the embryonic stem cell test (EST). All DMSO-extracts of HFO inhibit ES-D3 cell differentiation in a concentration-dependent manner and their potency is proportional to the amount of 3-7 ring PAHs they contain. All DMSO-extracts of HFOs also show aryl hydrocarbon receptor (AhR)-mediated activities, as tested in the AhR-CALUX assay. Contrarily, the HRBO-extract tested negative in both assays. Co-exposure of ES-D3 cells with selected DMSO-extracts of PS and the AhR-antagonist trimethoxyflavone, successfully counteracted the PS-induced inhibition of ES-D3 cell differentiation, confirming the role of the AhR in mediating the observed PDT of PS extracts in the EST. A good correlation exists when comparing the in-vitro with the in-vivo PDT potencies of the PS under study. Altogether, our findings corroborate the hypothesis that PS-induced PDT is caused by 3-7 ring PAHs present in these substances and that the observed PDT is partially AhR-mediated.


Assuntos
Células-Tronco Embrionárias/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Petróleo/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Receptores de Hidrocarboneto Arílico/metabolismo , Bioensaio , Poluentes Ambientais/metabolismo , Feminino , Humanos , Petróleo/metabolismo , Gravidez
3.
Environ Res ; 177: 108641, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421445

RESUMO

Lead (Pb) is a worldwide environmental contaminant that even at low levels influences brain development and affects neurobehavior later in life; nevertheless it is only a small fraction of the neurotoxicant (NT) exposome. Exposure to environmental Pb concurrent with other NT substances is often the norm, but their joint effects are challenging to study during early life. The aim of this review is to integrate studies of Pb-containing NT mixtures during the early life and neurodevelopment outcomes of children. The Pb-containing NT mixtures that have been most studied involve other metals (Mn, Al, Hg, Cd), metalloids (As), halogen (F), and organo-halogen pollutants. Co-occurring Pb-associated exposures during pregnancy and lactation depend on the environmental sources and the metabolism and half-life of the specific NT contaminant; but offspring neurobehavioral outcomes are also influenced by social stressors. Nevertheless, Pb-associated effects from prenatal exposure portend a continued burden on measurable neurodevelopment; they thus favor increased neurological health issues, decrements in neurobehavioral tests and reductions in the quality of life. Neurobehavioral test outcomes measured in the first 1000 days showed Pb-associated negative outcomes were frequently noticed in infants (<6 months). In older (preschool and school) children studies showed more variations in NT mixtures, children's age, and sensitivity and/or specificity of neurobehavioral tests; these variations and choice of statistical model (individual NT stressor or collective effect of mixture) may explain inconsistencies. Multiple exposures to NT mixtures in children diagnosed with 'autism spectrum disorders' (ASD) and 'attention deficit and hyperactivity disorders' (ADHD), strongly suggest a Pb-associated effect. Mixture potency (number or associated NT components and respective concentrations) and time (duration and developmental stage) of exposure often showed a measurable impact on neurodevelopment; however, net effects, reversibility and/or predictability of delays are insufficiently studied and need urgent attention. Nevertheless, neurodevelopment delays can be prevented and/or attenuated if public health policies are implemented to protect the unborn and the young child.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Lactente , Gravidez , Qualidade de Vida
4.
Toxicol Lett ; 314: 43-52, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31310794

RESUMO

Thioredoxin is an evolutionarily conserved antioxidant protein that plays a crucial role for fundamental cellular processes and embryonic development. Growing evidence support that Thioredoxin influences cellular response to chemicals insults, particularly those accompanying oxidative stress. The mechanisms underlying the functions of Thioredoxin1 in the embryonic development under the environmental toxicant exposure remain, however, largely unexplored. We report here that thioredoxin1 becomes differentially expressed in zebrafish embryos after exposure to 9 out of 11 environmental chemicals. In situ gene expression analysis show that thioredoxin1 is expressed in neurons, olfactory epithelia, liver and swim bladder under normal conditions. After MeHg exposure, however, thioredoxin1 is ectopically induced in the hair cells of the lateral line and in epithelia cells of the pharynx. Knockdown of Thioredoxin1 induces hydrocephalus and increases cell apoptosis in the brain ventricular epithelia cells. In comparison with 5% malformation in embryos injected with control morpholino, MeHg induces more than 77% defects in Thioredoxin1 knockdown embryos. Our data suggest that there is an association between hydrocephalus and Thioredoxin1 malfunction in embryonic development, and provide valuable information to elucidate the protective role of Thioredoxin1 against chemicals disruption.


Assuntos
Encéfalo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Hidrocefalia/induzido quimicamente , Tiorredoxinas/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Apoptose/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica no Desenvolvimento , Hidrocefalia/embriologia , Hidrocefalia/genética , Hidrocefalia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Tiorredoxinas/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
5.
Environ Sci Pollut Res Int ; 26(23): 23453-23459, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201704

RESUMO

Cadmium (Cd) as a widespread toxic heavy metal accumulates in animal food including chicken meat through food chain enrichment and finally threatens human health. Selenium (Se) is an essential mineral and possesses antagonistic effects on Cd-induced multiple organs' toxicity in chickens. The objective of the present study was to reveal the antagonistic mechanisms of Se to Cd from the aspects of oxidative stress, inflammation, and meat quality in chicken breast muscles. Firstly, the results showed that Cd significantly elevated the levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and protein carbonyl, and declined the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) to trigger oxidative stress in chicken breast muscles. However, Se treatment significantly alleviated Cd-induced oxidative stress by increasing the levels of GSH-Px, SOD, and CAT, and decreasing the levels of MDA, H2O2, and protein carbonyl. Secondly, Se obviously inhibited the expressions of Cd-activated inflammation-related genes including tumor necrosis factor (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (COX-2), and prostaglandin E synthase (PTGEs) in chicken breast muscles. Thirdly, meat quality-related parameters including pH45min, ultimate pH (pHu), and drip loss were also detected, and the results showed that Se markedly recovered Cd-induced dropt of pH45min and increase of drip loss in chicken breast muscles. In brief, these findings demonstrated that Se significantly alleviated Cd-induced oxidative stress and inflammation, and declined meat quality of chicken breast muscles.


Assuntos
Antioxidantes/metabolismo , Cádmio/toxicidade , Galinhas/fisiologia , Poluentes Ambientais/toxicidade , Carne/análise , Selênio/metabolismo , Animais , Cádmio/metabolismo , Catalase/metabolismo , Galinhas/metabolismo , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
6.
Environ Pollut ; 251: 871-878, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234252

RESUMO

Di(2-ethylhexyl)phthalate (DEHP) is an ubiquitous and emerging contaminant that is widely present in food, agricultural crop, and the environment, posing a potential risk to human health. This study utilized the nematode Caenorhabditis elegans to decipher the toxic effects of early life exposure to DEHP on aging and its underlying mechanisms. The results showed that exposure to DEHP at 0.1 and 1.5 mg/L inhibited locomotive behaviors. In addition, DEHP exposure significantly shortened the mean lifespan of the worms and further adversely affected pharyngeal pumping rate and defecation cycle in aged worms. Moreover, DEHP exposure also further enhanced accumulation of age-related biomarkers including lipofuscin, lipid peroxidation, and intracellular reactive oxygen species in aged worms. In addition, exposure to DEHP significantly suppressed gene expression of hsp-16.1, hsp-16.49, and hsp-70 in aged worms. Further evidences showed that mutation of genes involved in insulin/IGF-1-like signaling (IIS) pathway (daf-2, age-1, pdk-1, akt-1, akt-2, and daf-16) restored lipid peroxidation accumulation upon DEHP exposure in aged worms, whereas skn-1 mutation resulted in enhanced lipid peroxidation accumulation. Therefore, IIS and SKN-1 may serve as an important molecular basis for DEHP-induced age-related declines in C. elegans. Since IIS and SKN-1 are highly conserved among species, the age-related declines caused by DEHP exposure may not be exclusive in C. elegans, leading to adverse human health consequences due to widespread and persistent DEHP contamination in the environment.


Assuntos
Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Dietilexilftalato/toxicidade , Poluentes Ambientais/toxicidade , Fator de Crescimento Insulin-Like I/metabolismo , Longevidade/efeitos dos fármacos , Plastificantes/toxicidade , Animais , Biomarcadores/metabolismo , Proteínas de Caenorhabditis elegans/biossíntese , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Choque Térmico/biossíntese , Insulina/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipofuscina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética
7.
Environ Pollut ; 251: 984-989, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234266

RESUMO

Di(2-ethylhexyl) phthalate (DEHP), as a widely used plasticizer, is reported to have widespread environmental and global health hazards. Trace amounts of phthalates in the environment are sufficient to disrupt ecological balance and affect human health. However, DEHP-induced splenic toxicity remains in an unknown state. Therefore, to explore the mechanism of DEHP-induced splenic toxicity, male quail were employed with 0, 250, 500 and 750 mg/kg body weight DEHP by daily gastric perfusion for 45 days. Notably, splenic corpuscular border and cell gap enlargement were observed in the spleen tissue of DEHP-exposed quail under the histopathological analysis. Furthermore, DEHP induced dysregulation of oxidative stress markers by increasing malondialdehyde (MDA) content and decreasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. Low concentration of DEHP (≤250 mg/kg) exposure suppressed nuclear factor-E2-related factor 2 (Nrf2) signaling pathway, while high concentration of DEHP (≥500 mg/kg) exposure activated Nrf2-mediated defense response. DEHP induced splenic oxidative stress via interfering Nrf2 signal pathway and altering the transcription of its downstream genes. In conclusion, this study suggested that DEHP induced splenic toxicity.


Assuntos
Coturnix/fisiologia , Dietilexilftalato/toxicidade , Poluentes Ambientais/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Plastificantes/toxicidade , Baço/patologia , Animais , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ácidos Ftálicos , Transdução de Sinais , Superóxido Dismutase/metabolismo
8.
Chemosphere ; 232: 471-480, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31163323

RESUMO

Pesticide residues in beebread, live and dead honey bees, together with honey bee death rate were monitored from June 2016 to June 2018 in three apiaries, located near agricultural settings and in wildlands. Dead honey bees were only collected and analyzed when significant mortality episodes occurred and pesticide content in beeswax of each experimental apiary was evaluated at the beginning of the study. Samples were extracted by a modified QuEChERS procedure and screened for pesticides residues by liquid chromatography mass spectrometry (LC-MS/MS). Pesticide hazard in the samples was evaluated through the hazard quotient approach (HQ). Beebread was widely contaminated with coumaphos and amitraz degradate 2, 4-dimethylphenylformamide (DMF), miticides detected in 94 and 97% of samples respectively. However, insecticides sprayed during citrus bloom like chlorpyrifos (up to 167 ng g -1) and dimethoate (up to 34 ng g -1) were the main responsible of the relevant pesticide hazard in this matrix. Pesticide levels in live bees were mostly residual, and pesticide hazard was low. Beeswax of the apiaries, contaminated by miticides, revealed a low pesticide hazard to honey bee colonies. Acute mortality episodes occurred only in the two apiaries located near agricultural settings. Dead bees collected during these episodes revealed high levels (up to 2700 ng g -1) of chlorpyrifos, dimethoate, omethoate and imidacloprid. HQ calculated in dead bees exceeded up to 37 times the threshold value considered as elevated hazard to honey bee health.


Assuntos
Abelhas/efeitos dos fármacos , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Inseticidas/análise , Resíduos de Praguicidas/análise , Acaricidas/análise , Acaricidas/envenenamento , Agricultura , Animais , Abelhas/química , Abelhas/crescimento & desenvolvimento , Monitoramento Ambiental/instrumentação , Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Resíduos de Praguicidas/toxicidade , Própole/química , Espanha , Análise de Sobrevida , Ceras/química
9.
Environ Pollut ; 246: 904-913, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159140

RESUMO

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in environmental media and biological samples. However, knowledge of its adverse health consequences is limited. In the current study, Caenorhabditis elegans (C. elegans, L1 larvae) were exposed to TDCPP at environmentally relevant concentrations (control, 0.1, 1, 100 and 1000 µg L-1) for 72 h to explore any association between TDCPP and the aging process. Some of the degenerative age-related indicators were observed, including locomotion behaviors and lifespan. As crucial biomarkers of aging, the accumulation of lipofuscin, and lipid peroxidation (LPO) products exemplified by 4-hydroxynon-2-enal (4-HNE) were detected. This product forms as a result of oxidative stress, as confirmed by an N-acetyl-L-cysteine (NAC) pharmacological assay. Moreover, a significant increase in reactive oxide species (ROS) production in a dose-dependent manner using a fluorescent probe was observed. For the underlying molecular mechanism of the above aging phenotypes, significantly upregulated transcription of genes related to antioxidant systems, especially a subset of glutathione S-transferase (gst-5, gst-6, gst-9, gst-10, gst-19, gst-24, gst-26, gst-29, gst-33, and gst-38), was found by RNA-Seq and further confirmed by RT-qPCR. The elevated glutathione S-transferase (GST) was attributed to the significant increase in 4-HNE because mutations in gst-5 and gst-24 inhibited the conjugation of GSTs with 4-HNE. Therefore, GST play an indispensable role in the detoxification process of TDCPP exposure and further confirmed LPO accumulation at the molecular mechanism level. In conclusion, TDCPP accelerated the aging process induced by the LPO products, 4-HNE, response to reactive oxidative species in C. elegans.


Assuntos
Envelhecimento/efeitos dos fármacos , Aldeídos/metabolismo , Poluentes Ambientais/toxicidade , Compostos Organofosforados/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Caenorhabditis elegans/fisiologia , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo
10.
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
11.
Environ Pollut ; 246: 945-954, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159144

RESUMO

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and hazardous to human health. Aflatoxin B1 (AFB1) is a strong carcinogen dependent on activation by cytochrome P450 (CYP) 1A2 and 3A4. Humans in some regions may be exposed to both PCBs and AFB1. Since PCBs are CYP inducers, we were interested in their combined genotoxicity. In this study, the effects of non-coplanar 2,3,3'-tri- (PCB 20), 2,2'5,5'-tetra- (PCB 52), 2,3,3',4'-tetrachlorobiphenyl (PCB 56), and coplanar 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on protein levels of CYP1A1, 1A2, and 3A4, and nuclear receptors AhR, CAR and PXR in a human hepatocyte (L-02) line were investigated. Moreover, the combined effects of each PCB and AFB1 for induction of micronuclei and double-strand DNA breaks (indicated by an elevation of γ-H2AX) were analyzed. The results indicated that PCBs 20, 52 and 56 reduced the expression of AhR, while elevated that of CAR and PXR, with thresholds at low micromolar concentrations. However, they were less potent than PCB 126, which was active at sub-nanomolar levels. Overexpression of human splice variant CAR 3 in the cells increased CYP1A2 and 3A4 levels, which were further enhanced by each non-coplanar PCB, suggesting a role of CAR in modulating CYPs. Pretreatment of cells with each test PCB potentiated both micronuclei formation and DNA damage induced by AFB1. This study suggests that both non-coplanar and coplanar PCBs may enhance the genotoxicity of AFB1, through acting on various nuclear receptors; the potentiation of AFB1 genotoxicity by PCBs and the potential health implications may deserve concerns and further investigation.


Assuntos
Aflatoxina B1/toxicidade , Carcinógenos/toxicidade , Sistema Enzimático do Citocromo P-450/genética , Poluentes Ambientais/toxicidade , Bifenilos Policlorados/toxicidade , Linhagem Celular , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP3A/genética , Poluentes Ambientais/química , Hepatócitos/efeitos dos fármacos , Humanos , Bifenilos Policlorados/química , Receptores Citoplasmáticos e Nucleares/genética
12.
Environ Pollut ; 246: 955-962, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159145

RESUMO

Perfluorooctanoic acid (PFOA) toxicity is of considerable concern due to its wide application, environmental persistence, and bioaccumulation. In the current study, we used a scaffold-free three-dimensional (3D) spheroid model of mouse liver cells (AML12) to explore the toxicity of PFOA and emerging alternatives (HFPO-DA and PFO4DA). Comparing the short-term (24 and 72 h treatment) toxicity of PFOA between conventional 2D monolayer cells and 3D spheroids, we found that spheroids had higher EC50 values and lower ROS levels after treatment, indicating their greater resistance to PFOA. Cell viability (i.e., adenosine triphosphate (ATP) content and lactate dehydrogenase (LDH) leakage) and liver-specific function (i.e., albumin secretion) were stable in spheroids through 28 day of culture. However, under 100 and 200 µM-PFOA treatment for 28 day, ROS levels, LDH leakage, and caspase3/7 activity all increased significantly. As a sensitive parameter, ROS showed a significant increase at 21 day, even in the 50 µM-PFOA group. Consistent with the elevation of ROS and caspase3/7, the expressions of oxidative stress- and apoptosis-related genes, including Gsta2, Nqo1, Ho-1, caspase3, p53, and p21, were induced in dose- and time-dependent manners after PFOA exposure. The peroxisome proliferator-activated receptor alpha (PPARα) pathway was also activated after treatment, with significant induction of its target genes, Fabp4 and Scd1. Similar to PFOA, both HFPO-DA and PFO4DA activated the PPARα pathway, induced ROS levels, and initiated cell damage, though at a relatively lower extent than that of PFOA. Our results imply that the 3D spheroid model is a valuable tool in chronic toxicological studies.


Assuntos
Caprilatos/toxicidade , Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Fígado/efeitos dos fármacos , Modelos Biológicos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Caprilatos/química , Linhagem Celular , Poluentes Ambientais/química , Fluorcarbonetos/química , Fígado/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , PPAR alfa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
13.
Environ Pollut ; 246: 963-971, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159146

RESUMO

Bisphenol S (BPS) has been widely used as a bisphenol alternative in recent few years. However, with mounting evidence suggesting that the presence of BPS in the environment also poses risks to ecosystems and human health, we decided to use the juvenile common carp (Cyprinus carpio) and its primary macrophages as in vivo and in vitro models to examine if BPS is a safe substitute of BPA. The present study evaluated the immune responses of chronic BPS exposure and their mechanisms of action associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway. Potential oxidative stress and pro-inflammatory effects of BPS exposure were identified in fish liver after 60-day exposure, based on the increased reactive oxygen species (ROS) production, antioxidant capacity, NO production, lipid peroxidation, and induction of inflammatory cytokine expression, as well as acute phase protein levels of C-reactive protein, immunoglobulin M, lysozyme, and complement component 3. Moreover, pparγ, PPAR pathway-associated genes retinoid x receptor α (rxrα) and nuclear factor-κb (nfκb) presented a rough concentration-dependent alteration after BPS exposure. An acute BPS exposure to the isolated primary macrophages from juvenile common carp was performed to help elucidate gene expression patterns of pparγ, rxrα, and nfκb in a typical immune cell model, the results were consistent with what we found in vivo experiments for long-term BPS exposure. Furthermore, with coexposure to BPS and a PPARγ antagonist, the restriction of PPAR signaling pathway significantly inhibited the induction of ROS and the mRNA level of interleukin-1ß, confirming the involvement of PPAR pathway in BPS-induced chronic inflammatory stress in liver.


Assuntos
Poluentes Ambientais/toxicidade , Inflamação/metabolismo , Fígado/efeitos dos fármacos , PPAR gama/metabolismo , Fenóis/toxicidade , Sulfonas/toxicidade , Animais , Carpas/imunologia , Carpas/metabolismo , Inflamação/genética , Fígado/imunologia , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
14.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(6): 645-652, 2019 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-31177766

RESUMO

Dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene are common organic pollutants in food. They have been of concern to academics and government administrations due to high residue and persistence, easy accumulation and strong harmful effects. The National Research Council of the United States of America published Toxicity Testing in the 21st Century: A Vision and Strategy in 2007, which proposed a new concept of toxicity testing that toxicity testing should take full consideration of population exposure data and base on in vitro tests, human cell lines, toxicity pathways and high-throughput screening. Meanwhile, systems biology, bioinformatics and rapid assay technologies will be used to better understand toxicity pathways-the cellular response pathways that can lead to adverse health effects when sufficient perturbing induced by chemicals exposure. The new toxicity testing strategy has changed the traditional testing pattern and has brought a wide impact on the international relevant fields. The European Union, the World Health Organization, and the United States Environmental Protection Agency, the Food and Drug Administration, and the National Center for Toxicological Research have organized relevant discussions and exploratory studies to address the new toxicity testing concept and how to evaluate and utilize the results of traditional toxicity test researches. Compared to the discussion, 'whether to do it', ten years ago, the question, 'how to do it', has become the concern of the current discussion. Therefore, how to respond to the concept of toxicity testing and how to effectively utilize and excavate traditional toxicity test data have been the focus of multi-disciplines and interdisciplinary academia such as toxicology, food hygiene and environmental science. Therefore, this article provides an overview of the exposure levels of dioxin, polybrominated diphenyl ethers and benzo[a]pyrene, which are typical persistent organic pollutants in food in China and the current research status of toxic pathways based on whole animal experiments. The exposure level, toxic effect and toxicity mechanism of three contaminants are analyzed and summarized in order to provide basis for future results based on the 21st century toxicity test compared with traditional tests and data mining analysis of these two kinds of data. Meanwhile, it also lays the foundation for the establishment of a toxicity testing framework based on exposure characteristics, toxic pathways, and biomarkers.


Assuntos
Poluentes Ambientais , Contaminação de Alimentos , Dibenzodioxinas Policloradas , Animais , China , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Humanos , Compostos Orgânicos/análise , Compostos Orgânicos/toxicidade , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/toxicidade , Pesquisa , Testes de Toxicidade
15.
Ecotoxicol Environ Saf ; 181: 224-230, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31195231

RESUMO

Cadmium (Cd), as a kind of ubiquitous and highly toxic heavy metal pollutants, has been known to result in immunotoxicity in animals. As a multifunctional bioactivity disaccharide, trehalose (Tre) is characterized by antioxidative, antiapoptotic, and accelerating autophagy. In this study, Sprague-Dawley (SD) rats were fed with cadmium chloride (CdCl2) and/or Tre to explore the molecular mechanisms of Tre-protected against spleen injury caused by Cd exposure. Firstly, the results showed that Tre partially recovered splenic pathological changes induced by Cd exposure. Secondly, Tre dramatically declined the level of methane dicarboxylic aldehyde (MDA) and elevated the level of total antioxidant capacity (T-AOC) to weaken oxidative stress caused by Cd exposure in spleen tissue. Moreover, the results showed that Tre significantly suppressed Cd-induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulated the protein expression of nuclear Nrf2. Thirdly, Tre remarkably reduced the protein expression of sequestosome 1 (p62/SQSTM1) and microtubule-associated protein light chain 3II (LC-3II) to restore autophagy inhibition induced by Cd exposure. Finally, the results of TUNEL and the expression of apoptosis marker proteins showed that Tre significantly inhibited Cd-induced apoptosis in spleen tissue to exert its protective effects. In summary, the results indicated that Tre modulated Nrf2 signaling pathway, which interacted with apoptosis and autophagy to against Cd-induced spleen injury, providing potential therapeutic strategies for the prevention and treatment of Cd-related immune system diseases.


Assuntos
Cloreto de Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Baço/efeitos dos fármacos , Trealose/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Baço/metabolismo , Baço/patologia
16.
Ecotoxicol Environ Saf ; 181: 370-380, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31212185

RESUMO

Cigarette smoke can cause follicle destruction and oocyte dysfunction and increase the risks of spontaneous abortion, stillbirth, and tubal ectopic pregnancy, affecting female reproductive health. Third-hand smoke (THS) is residual tobacco smoke existing in the environment long after cigarettes are extinguished, which can react with other compounds in the environment to produce secondary pollutants. However, the effects of THS on the female reproductive system, particularly the maturation of the oocyte, remain unclear. 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a component of THS, is a logical biomarker of THS exposure. Thus, this study aims to investigate the toxic effects of NNA on the maturation of murine oocytes and subsequent developmental competence. Herein, murine oocytes were exposed to 0 (control group), 0.1, 1.0, 10, and 50 µM NNA for 24 h. Our results showed that NNA exposure reduced the polar body extrusion rate by causing 8-oxo-deoxyguanosine (8-OHdG) to increase and disrupting the meiotic spindle morphology by inhibiting ERK1/2 activation during in vitro maturation. Additionally, NNA exposure resulted in cleavage and blastocyst rate reduction by altering DNA and histone methylations by reducing 5 mC and H3K4me2 levels and by inducing apoptosis caused by mitochondrial dysfunction and reactive oxygen species accumulation, as shown by the increased superoxide dismutase mRNA level and by the decreased Bcl-x mRNA level. Collectively, our results demonstrate that NNA exposure reduces the maturation and developmental capability of murine oocytes by increasing the risk of DNA damage and abnormal spindle morphology, altering epigenetic modifications, and inducing apoptosis, suggesting the toxic effect of NNA on mammalian productive health.


Assuntos
Poluentes Ambientais/toxicidade , Nitrosaminas/toxicidade , Oócitos/efeitos dos fármacos , Animais , Apoptose , Dano ao DNA , Epigênese Genética , Feminino , Camundongos , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fuso Acromático/efeitos dos fármacos
17.
Biomed Environ Sci ; 32(4): 281-290, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31217064

RESUMO

OBJECTIVE: The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant, is harmful to the nervous system, but its effects on the brain are still unclear. This study aimed to investigate the effects of TCDD on astrocytes proliferation and underlying molecular mechanism. METHODS: The cell proliferation was measured by EdU-based proliferation assay and PI staining by flow cytometry. Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of signal transducer and activator of transcription 3 (STAT3). RESULTS: C6 cells treated with 10 and 50 nmol/L TCDD for 24 h showed significant promotion of the proliferation of. The exposure to TCDD resulted in the upregulation in the expression levels of phosphorylated protein kinase B (p-Akt), phosphorylated STAT3, and cyclin D1 in a dose- and time-dependent manner. The inhibition of Akt expression with LY294002 or STAT3 expression with AG490 abolished the TCDD-induced cyclin D1 upregulation and cell proliferation. Furthermore, LY294002 suppressed the activation of STAT3. Finally, TCDD promoted the translocation of STAT3 from the cytoplasm to the nucleus, and LY294002 treatment blocked this effect. CONCLUSION: TCDD exposure promotes the proliferation of astrocyte cells via the Akt/STAT3/cyclin D1 pathway, leading to astrogliosis.


Assuntos
Astrócitos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Neurotoxinas/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Animais , Animais Recém-Nascidos , Ciclina D1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo
18.
Aquat Toxicol ; 213: 105216, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31185428

RESUMO

Ecotoxicological studies relating to tire wear particles (TWP) have focussed, up until very recently, almost entirely on the released leachate. Little is known about the toxicology effects of TWP dispersed in freshwater. In the present small-scale study we exposed Hyallela azteca to TWP dispersed in water with the aim of (i) determining the potential acute and chronic impacts of TWP exposure (ii) challenging the prevailing idea that tire leachate is the primary causative agent of tire-related toxicity. H. azteca were shown to indescriminately ingest TWP with a gut retention time of 24-48 h. Acute (48 h) TWP exposure followed an expected concentration-response curve from which an LC50 of 3426 ± 172 particles mL-1 was determined, but leachate exposure did not conform to a sigmoidal concentration-response pattern and therefore an LC50 was not derivable. However, toxicity profiles of TWP and leachate appeared to be sufficiently different as to suggest a dissimilar mechanism of toxicity. Mortality, reproductive output (neonate production) and net growth were all significantly impacted at the higher exposure concentrations (500-2000 particles mL-1) following 21 days exposure. Our study demonstrates that TWP exposure elicits short-term and longer-term toxicity on a key freshwater organism.


Assuntos
Anfípodes/fisiologia , Poluentes Ambientais/toxicidade , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Anfípodes/efeitos dos fármacos , Animais , Ecotoxicologia , Humanos , Dose Letal Mediana , Fatores de Tempo , Poluentes Químicos da Água/toxicidade
19.
Sci Total Environ ; 686: 893-902, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31200309

RESUMO

Hexabromocyclododecane (HBCD) is a widely applied brominated flame retardant (BFR) and is regarded as a persistent organic pollutant. It has been found in human tissues and has the potential to cause neurological disorders. However, our understanding of HBCD neurotoxicity at the diastereoisomer level remains lacking. Here, we investigated the neurotoxicity of three HBCD diastereoisomers, i.e., α-, ß-, and γ-HBCD, in SH-SY5Y human neuroblastoma cells. Results showed that the HBCD diastereoisomers decreased cell viability, increased lactate dehydrogenase (LDH) release, and impaired cytoskeleton development. Typical morphological features and apoptosis rates showed that the HBCD diastereoisomers induced SH-SY5Y cell apoptosis. The expression levels of several cell apoptosis-related genes and proteins, including Bax, caspase-3, caspase-9, cytochrome c, Bcl-2, and X-linked inhibitor of apoptosis (XIAP), as well as the cell cycle arrest, DNA damage, adenosine triphosphate (ATP) consumption, reactive oxygen species (ROS) levels, and intracellular calcium ion (Ca2+) levels, were examined. Results showed that the HBCD diastereoisomer neurotoxicity was ranked ß-HBCD > γ-HBCD > α-HBCD. The cell apoptosis and caspase expression levels of the three HBCD diastereoisomers followed the same order, suggesting that caspase-dependent apoptosis may be one mechanism responsible for the structure-selective HBCD diastereoisomer neurotoxicity. The levels of intracellular Ca2+ and ROS increased significantly. The ROS levels were ordered ß-HBCD > γ-HBCD > α-HBCD, whereas those of intracellular Ca2+ were γ-HBCD > ß-HBCD > α-HBCD. Thus, ROS may be a key factor regulating the neurotoxicity of HBCD diastereoisomers. To the best of our knowledge, this is the first study to report on the diastereoisomer-specific toxicity of HBCD in human neural cells and on the possible mechanisms responsible for the selective neurotoxicity of HBCD diastereoisomers.


Assuntos
Poluentes Ambientais/toxicidade , Hidrocarbonetos Bromados/toxicidade , Sistema Nervoso/efeitos dos fármacos , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Dano ao DNA , Retardadores de Chama , Humanos , Neuroblastoma , Proteínas Proto-Oncogênicas c-bcl-2 , Espécies Reativas de Oxigênio , Testes de Toxicidade
20.
Chemosphere ; 233: 25-33, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31163305

RESUMO

Poly and perfluoroalkyl substances (PFAS) are a large group of emerging organic pollutants that can persist in the environment and bioaccumulate in biota. They are found in complex mixtures, and although the exact number of PFAS is unknown, it has been estimated to be in the thousands. The objective of this study was two-fold. First, we examined the cytotoxicity of PFAS singly and in binary mixtures using an amphibian fibroblast cell line. Second, we used this experimental data to develop quantitative structure-activity relationship (QSAR) models for single and binary mixtures. We tested the cytotoxicity of four common PFAS: perfluorooctane sulfonate (PFOS); perfluorooctanoic acid (PFOA); perfluorohexane sulfonate (PFHxS); and perfluorohexanoic acid (PFHxA). PFOS was the most toxic and PFHxA the least cytotoxic. Binary mixtures allowed for the construction of isobolograms to test for additivity, synergism, or antagonism. Using this data, QSAR modeling was used for predicting the toxicity of 24 single and 1380 binary mixtures (theoretically generated). Overall, our experimental and modeling results showed that mixtures were approximately additive, with the exception of PFOS and PFOA, which were found to be weakly synergistic. This data shows that certain mixtures of PFAS may have increased toxicity potential above what the simple sum of PFAS concentrations would suggest. More studies are needed that test the toxicity of PFAS mixtures.


Assuntos
Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Testes de Toxicidade , Ácidos Alcanossulfônicos/toxicidade , Anfíbios , Animais , Caproatos/toxicidade , Caprilatos/toxicidade , Linhagem Celular , Simulação por Computador , Fibroblastos , Técnicas In Vitro
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