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1.
Ecotoxicol Environ Saf ; 203: 111041, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888612

RESUMO

Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.


Assuntos
Dislipidemias/induzido quimicamente , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/induzido quimicamente , Bifenilos Policlorados/toxicidade , Animais , Biomarcadores/análise , Colo/microbiologia , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Feminino , Conteúdo Gastrointestinal/microbiologia , Microbioma Gastrointestinal/genética , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , RNA Ribossômico 16S
2.
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
3.
Sci Total Environ ; 745: 141140, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-32736114

RESUMO

Polychlorinated biphenyls (PCBs) have been reported to pose a severe risk towards human health, and hydroxylated polychlorinated biphenyls (OH-PCBs) were potential substances basis for PCBs' toxicity. This study aims to determine the inhibition of OH-PCBs towards human carboxylesterases (CESs), including CES1 and CES2. For phenotypic analysis of CES1 and CES2 activity, we used the hydrolysis metabolism of 2-(2-benzoyl3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) catalyzed by human liver microsomes (HLMs) as the probe reactions. Preliminary inhibition screening showed that the inhibition potential of OH-PCBs towards CES1 and CES2 increased with the increased numbers of chlorine atoms in OH-PCBs. Both 2'-OH-PCB61 and 2'-OH-PCB65 showed concentration-dependent inhibition towards both CES1 and CES2. Lineweaver-Burk plots showed that 2'-OH-PCB61 and 2'-OH-PCB65 exerted non-competitive inhibition towards CES1 and competitive inhibition towards CES2. The inhibition kinetics parameters (Ki) were 6.8 µM and 7.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES1, respectively. The inhibition kinetics parameters (Ki) were 1.4 µM and 1.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES2, respectively. In silico docking methods elucidate the contribution of hydrogen bonds and hydrophobic contacts towards the binding of 2'-OH-PCB61 and 2'-OH-PCB65 with CES1 and CES2. All these results will provide a new perspective for elucidation of toxicity mechanism of PCBs and OH-PCBs.


Assuntos
Hidrolases de Éster Carboxílico , Bifenilos Policlorados/toxicidade , Carboxilesterase , Humanos , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Hidroxilação , Microssomos Hepáticos
4.
Ecotoxicol Environ Saf ; 204: 111063, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32791358

RESUMO

The lipocalins genes have been assigned for involving in the responses of organisms to various stress factors. The function of lipocalins under PCB18 stress was addressed by pathway complementation in the Oryza sativa L. OsTIL-silenced mutant. The growth of wild type (WT) and OsTIL-silenced mutant (MT) callus were suppressed by PCB18, and MT varieties were inhibited more seriously than WT varieties. Meanwhile, only WT varieties showed "Hormesis" effect. Compared with WT (3 day > 90.0%, 6 day ≤45.5%), MT varieties kept high removing efficiency by HPLC analysis. Varied gene transcription after OsTIL silencing was demonstrated between two varieties, especially obvious under PCB stress. Silenced OsTIL induced more protective gene transcriptions by qPCR analysis, OsVDE at 3 day, OsCHL, OsZEP1, OsZEP2 and OsUN at 6 day and OsZEP2 at 9 day. PCB18 stress further irritated these genes transcription in MT varieties. The defense stagy in WT varieties was that the transcriptions of lipocalins were inhibited to reduce PCB18 accumulation and toxicity. OsTIL could effectively limit PCB18 accumulation and toxicity. After TIL lacking, OsCHL, OsZEP1, OsZEP2 and OsUN in mutant were strongly evoked to against PCB stress. Remarkably, OsUN and OsZEP2 gene expressions were responded to PCB18 stress in both two varieties.


Assuntos
Poluentes Ambientais/toxicidade , Lipocalinas/genética , Oryza/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Ativação Transcricional/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Genes de Plantas , Oryza/genética , Oryza/crescimento & desenvolvimento , Estresse Oxidativo/genética
5.
Bull Environ Contam Toxicol ; 105(2): 250-254, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32666193

RESUMO

Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that pose a threat to environment and human health. Aiming at predicting PCBs risk in actual soil ecosystem, this study was conducted by chemical and biological methods to assess the bioavailability of PCBs in spiked soil, and in field-contaminated soils before or after remediation. The three chemical methods were Soxhlet, n-butanol and hydroxypropyl-ß-cyclodextrin (HPCD). Results were compared to actual PCB bioaccumulation in earthworms (Eisenia fetida). HPCD extraction was the best to predict the actual PCB bioaccumulation in all soils. The results suggest that HPCD could be an effective alternative method to earthworm toxicity test. This study provides strategy to understand the toxicity assessment in contaminated soil and soil after remediation.


Assuntos
Recuperação e Remediação Ambiental/métodos , Oligoquetos/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Poluentes do Solo/toxicidade , Solo/química , 1-Butanol/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Animais , Bioacumulação , Disponibilidade Biológica , China , Ecossistema , Fertilizantes/análise , Oligoquetos/química , Bifenilos Policlorados/análise , Solo/normas , Poluentes do Solo/análise , Testes de Toxicidade
6.
PLoS One ; 15(7): e0236394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702712

RESUMO

BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism. METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression. RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles. CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.


Assuntos
Criptorquidismo/sangue , Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Exposição Materna/efeitos adversos , Adulto , Estudos de Casos e Controles , Criptorquidismo/induzido quimicamente , Criptorquidismo/epidemiologia , Criptorquidismo/patologia , Diclorodifenil Dicloroetileno/sangue , Diclorodifenil Dicloroetileno/toxicidade , Poluentes Ambientais/toxicidade , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Hexaclorobenzeno/sangue , Hexaclorobenzeno/toxicidade , Humanos , Hidrocarbonetos Clorados/toxicidade , Recém-Nascido , Masculino , Bifenilos Policlorados/sangue , Bifenilos Policlorados/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Suécia/epidemiologia
7.
Chemosphere ; 260: 127609, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32693259

RESUMO

The environmental contaminant 3,3'-dichlorobiphenyl (PCB-11) is widely detected in environmental samples, and this parent compound along with its metabolites 4-OH-PCB-11 and 4-PCB-11-Sulfate are detected in human serum. Our previous research in zebrafish (Danio rerio) embryos shows exposure to 20 µM PCB-11 inhibits Cyp1a enzyme activity and perturbs lipid metabolism pathways. In this study, wildtype AB embryos underwent acute exposures from 1 to 4 days post fertilization (dpf) to 0.002-20 µM 4-OH-PCB-11 or 0.2-20 µM 4-PCB-11-Sulfate, with and without co-exposures to 100 µg/L benzo[a]pyrene (B[a]P) or 5 nM 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and were assessed for in vivo EROD activity and morphometrics. Chronic exposures from 1 to 15 dpf to assess lipid accumulation using Oil-Red-O staining were also conducted with 0.2 µM parent or metabolite compounds, alongside a co-exposure experiment of 0.002-0.2 µM 4-PCB-11-Sulfate and 10 µg/L B[a]P. For acute experiments, 2 and 20 µM 4-OH-PCB-11 was lethal but no Cyp1a or morphological effects were observed at lower concentrations; 20 µM 4-PCB-11-Sulfate significantly lowered the Cyp1a activity of B[a]P and PCB-126 but did not alter morphological development. For chronic experiments, 0.2 µM 4-PCB-11-Sulfate significantly increased lipid accumulation 30% in single exposures and 44% in co-exposures with B[a]P. Further long-term studies would better elucidate the effects of this contaminant, particularly in the context of environmentally-relevant mixtures.


Assuntos
Bifenilos Policlorados/toxicidade , Peixe-Zebra/fisiologia , Animais , Benzo(a)pireno/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Embrião não Mamífero/metabolismo , Larva/metabolismo , Lipídeos , Fígado/metabolismo , Bifenilos Policlorados/metabolismo , Sulfatos/metabolismo , Peixe-Zebra/metabolismo
8.
Environ Sci Technol ; 54(12): 7504-7512, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32459094

RESUMO

Using omics approaches to monitor complex environmental mixtures is challenging. Previously, we evaluated in vitro transcriptomic effects of complex organic extracts derived from avian eggs. However, there is a lack of studies using wild species that are naturally exposed to contaminant mixtures. Here, we examined polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) residues and gene expression in embryonic liver tissue of double-crested cormorants (Phalacrocorax auritus) collected from six variably contaminated colonies. Colonies near industrialized areas were distinguished from less contaminated sites based on their PCB and PBDE concentrations. The most variably expressed genes between sites were involved in pathways including, xenobiotic metabolism (e.g., Cyp1a4), lipid/bile acid homeostasis (e.g., Lbfabp), and oxidative stress (e.g., Mt4). Hierarchical clustering, based on relative gene expression, revealed a grouping pattern similar to chemical residue concentrations. Further, partial least squares regression analysis was used to estimate chemical concentrations from transcriptomics data. PCB 155 and BDE 47 showed the highest slopes (0.77 and 0.69, respectively) fitted by linear regression of measured and estimated chemical concentrations. The application of transcriptomics to a wild avian species, naturally exposed to complex chemical mixtures and other stressors, represents a promising means to distinguish and prioritize variably contaminated sites.


Assuntos
Lagos , Bifenilos Policlorados , Animais , Aves/genética , Monitoramento Ambiental , Óvulo/química , Bifenilos Policlorados/análise , Bifenilos Policlorados/toxicidade , Toxicogenética
9.
Arch Environ Contam Toxicol ; 79(1): 122-130, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32300848

RESUMO

Exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) through food, water, and air occurred during the life, which may change telomere length (TL) in peripheral blood leukocytes. The present study was designed to investigate the association between TL and serum levels of PCBs and OCPs in Tehran male's population. Whole blood samples were randomly taken from 300 adult males, aged between 25 and 40 years. TL was determined by real-time PCR to measure the number of the telomere (T) repeats to the number of a single-copy gene (S). We applied the multivariate linear regression model to compare the effect of each lipid adjusted serum levels of PCBs and OCPs congener on the TL, with adjustment for age, body mass index, education, smoking, and food patterns. Each doubling of the nondioxin-like PCBs, dioxin-like PCBs, and OCPs levels were associated with 1.9% [95% confidence interval (CI) - 0.70 to 5.40%], 2.5% (95% CI 0.30-8.3%), and - 2.4% (95% CI - 0.70 to - 6.2%) variation in the TL, respectively. The percent difference in the TL with exposure to nondioxin-like PCBs, dioxin-like PCBs, and OCPs for participants with older than age 37 years were 6.45% (95% CI 2.81-16.50%), 4.52% (95% CI 1.60-10.54%), and - 7.44% (95% CI - 1.55 to - 15.51%), respectively. Exposures to nondioxin-like PCBs (except for PCB 28 and 52) with high chlorine in structure and dioxin-like PCBs were related to longer TLs. Conversely, serum levels of OCPs can be associated with oxidative stress and systemic inflammation that lead to telomere shortening.


Assuntos
Hidrocarbonetos Clorados/sangue , Leucócitos/efeitos dos fármacos , Praguicidas/sangue , Bifenilos Policlorados/sangue , Homeostase do Telômero/efeitos dos fármacos , Telômero/efeitos dos fármacos , Adulto , Fatores Etários , Humanos , Hidrocarbonetos Clorados/toxicidade , Irã (Geográfico) , Leucócitos/patologia , Lipídeos/sangue , Masculino , Praguicidas/toxicidade , Bifenilos Policlorados/toxicidade , Distribuição Aleatória , Inquéritos e Questionários
10.
Toxicology ; 437: 152438, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32199159

RESUMO

Polychlorinated biphenyls (PCBs) are persistent organic pollutants with human carcinogenicity. Many lower chlorinated and non-dioxin-like PCBs have been observed to be mutagenic following activation by human CYP2E1, while activation of dioxin-like (DL-) PCBs by this enzyme has never been evidenced. In this study, each DL-PCB was analyzed by molecular docking to human CYP2E1 protein for predicting a substrate interaction. All compounds demonstrated high affinities with the active site of human CYP2E1, binding energy being -8.7 ∼ -9.7 kcal/mol. However, most compounds demonstrated ligand-heme distances as ≥ 6.8 Å, while the values for 2,3,3',4,4'- (PCB 105) and 2,3',4,4',5-pentachlorobiphenyl (PCB 118) were 5.3 and 5.4 Å, respectively (valid for electron transfer). Experimentally, both PCB 105 and 118 induced micronuclei in a V79-derived cell line engineered for expression of human CYP2E1 at low micromolar concentrations, while inactive or weakly positive in V79-Mz control cells; these effects were blocked or reduced by 1-aminobenzotriazole, a suicide CYP inhibitor. However, DL-PCBs 77, 81 and 126 were all negative in both cell lines. In a human hepatoma (C3A) cell line, PCB 105 and 118 induced micronuclei marginally, while with ethanol pretreatment (to stabilize CYP2E1) both compounds induced micronuclei efficiently, and co-exposure to trans-1,2-dichloroethylene (a selective CYP2E1 inhibitor) led to clearly negative results with both compounds. Finally, both PCB 105 and 118 induced PIG-A gene mutations in C3A cells, which was blocked by trans-1,2-dichloroethylene. In summary, in silico and experimental results consistently suggest that DL- PCBs 105 and 118 may be activated by human CYP2E1 for mutagenic activities.


Assuntos
Citocromo P-450 CYP2E1/metabolismo , Proteínas de Membrana/genética , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Simulação de Acoplamento Molecular , Mutação , Bifenilos Policlorados/toxicidade , Ativação Metabólica , Animais , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Domínio Catalítico , Cricetulus , Citocromo P-450 CYP2E1/química , Citocromo P-450 CYP2E1/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Fibroblastos/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/patologia , Bifenilos Policlorados/química , Bifenilos Policlorados/metabolismo , Ligação Proteica , Conformação Proteica
11.
PLoS One ; 15(3): e0230283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191759

RESUMO

Polychlorinated biphenyls (PCBs) are worldwide chemical pollutants that have been linked to disrupted reproduction and altered sexual behaviour in many organisms. However, the effect of developmental PCB-exposure on adult passerine reproductive behaviour remains unknown. A commercial PCB mixture (Aroclor 1242) or an estrogenic congener (PCB 52) were administered in sublethal amounts to nestling zebra finches (Taeniopygia guttata) in the laboratory to identify effects of developmental PCB-exposure on adult zebra finch reproductive parameters. Results indicate that although traditional measures of reproductive success are not altered by this PCB dosage, PCBs do alter sexual behaviours such as male song and nesting behaviour. Males treated with PCB 52 in the nest sang significantly fewer syllables than control males, while females treated with Aroclor 1242 in the nest showed the strongest song preferences. PCB treatment also caused an increase in the number of nesting attempts and abandoned nests in the Aroclor 1242 treatment relative to the PCB 52 treatment, and offspring with control fathers fledged significantly earlier than those with fathers treated with Aroclor 1242. Behavioural differences between males seem to best explain these reproductive effects, most notably aggression. These findings suggest that sublethal PCB-exposure during development can significantly alter key reproductive characteristics of adult zebra finches, likely reducing fitness in the wild.


Assuntos
Comportamento Animal/efeitos dos fármacos , Exposição Ambiental , Tentilhões/crescimento & desenvolvimento , Bifenilos Policlorados/toxicidade , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/fisiologia , Feminino , Masculino , Comportamento de Nidação/efeitos dos fármacos , Vocalização Animal
12.
Ecotoxicol Environ Saf ; 194: 110338, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32135376

RESUMO

2,2',3,5',6-Pentachlorobiphenyl (PCB95) is known as a persistent pollutant that was found in eggs in China. PCB 95 can be metabolized into OH-PCB95 and MeO-PCB95 in liver microsomes. However, the toxicity and its mechanism of PCB95 or its metabolites have been little studied on laying hens. Herein, chicken embryo liver cells of laying hens were selected and treated with different levels of PCB95 and its two metabolites, and the EC50 of PCB95, OH-PCB95, MeO-PCB95 was 80.85, 4.81 and 107.04 µg/mL respectively, indicating that OH-PCB95 is much more cytotoxic than PCB95 or MeO-PCB95. Targeted metabolomics was further used to study the effects of the parent compound and its metabolites on cell metabolism. The results showed that four primary types of glycerophospholipids were down-regulated after exposure to PCB95 and its metabolites, especially PE and PS (60% more than the control for PCB95, 40% for OH-PCB95, and less than 40% for MeO-PCB95). KEGG pathway analysis based on amino acid metabolism showed that PCB95 may mainly interfere with the amino acids involved in immune regulation (phenylalanine and tyrosine), and OH-PCB95 may be associated with genetic disoders (cysteine, methionine and purine metabolism). However, the metabolic pathways induced by MeO-PCB95 are quite different from those induced by PCB95 and OH-PCB95, affecting mainly D-glutamine and D-glutamate metabolism, alanine and glutamate metabolism, and arginine and proline metabolism; these pathways mainly regulate the elimination of excess purines and are involved in the synthesis of the amino acids required by cells. These results showed that OH-PCB95 has the highest toxicity on chicken embryo liver cells and MeO-PCB95 could be a detoxification product of PCB95 and OH-PCB95. This study contributes to the understanding of the different effects of PCB95 and its metabolites on cellular metabolism, and the data are helpful in evaluating the hepatotoxic effects of these compounds.


Assuntos
Poluentes Ambientais/toxicidade , Bifenilos Policlorados/toxicidade , Aminoácidos/metabolismo , Animais , Embrião de Galinha , Galinhas/metabolismo , China , Ovos , Poluentes Ambientais/metabolismo , Feminino , Hepatócitos/metabolismo , Fígado/metabolismo , Redes e Vias Metabólicas , Metabolômica , Metionina/metabolismo , Microssomos Hepáticos/metabolismo , Testes de Toxicidade
13.
Environ Int ; 137: 105521, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007688

RESUMO

The lung has been reported to be one of the target organs of polychlorinated dibenzo-dioxins and polychlorinated dibenzo-furans (PCDD/Fs) in many toxicological studies. While the associations between PCDD/Fs exposure and lung function levels have not been investigated thoroughly. This study aimed to explore these associations and the potential mediating role of oxidative stress. In this study, 201 foundry workers and 222 non-exposed general residents were recruited from central China, and their lung function parameters were measured. Air and food samples were collected to determine the PCDD/Fs levels for individual PCDD/Fs exposure estimation. Serum PCDD/Fs levels were determined in a subgroup of individuals randomly selected from the study population to reflect the body burden. It was found that each 1-unit increase in ln-transformed concentration of PCDD/Fs exposure (fg TEQ/bw/day) was associated with a 0.47 L decrease in FVC and a 0.25 L decrease in FEV1. Each 1-unit increase in ln-transformed concentration of serum PCDD/Fs (fg TEQ/g lipid) was associated with a 0.36 L decrease in FVC and a 0.24 L decrease in FEV1. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was not only positively related to PCDD/Fs exposure, but also inversely associated with FVC and FEV1 are FVC (ß = -0.15, 95% CI: -0.22 to -0.08) and FEV1 (ß = -0.07, 95% CI: -0.13 to -0.02). Mediation analysis revealed that urinary 8-OHdG mediated 12.22% of the associations of external PCDD/Fs exposure with FVC levels, 28.61% and 27.87% of the associations of serum PCDD/Fs with FVC and FEV1 levels respectively. Our findings suggested that PCDD/Fs exposure was associated with decreased lung function levels by a mechanism partly involving oxidatively generated damage to DNA.


Assuntos
Dioxinas , Furanos , Pulmão , Estresse Oxidativo , Bifenilos Policlorados , Dibenzodioxinas Policloradas , China , Dibenzofuranos , Dibenzofuranos Policlorados/toxicidade , Dioxinas/toxicidade , Furanos/toxicidade , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Bifenilos Policlorados/toxicidade , Dibenzodioxinas Policloradas/toxicidade
14.
Arch Environ Contam Toxicol ; 78(4): 513-524, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32107597

RESUMO

Polychlorinated biphenyls (PCBs) are recognised reproductive and immune system toxicants in marine mammals mediated by endocrine-disrupting mechanisms. As with other predators, seals are exposed to elevated bioaccumulated concentrations of PCBs and other persistent organic pollutants (POPs). Cryopreserved plasma samples from adult ringed (Phoca hispida; n = 39) and grey (Halichoerus grypus; n = 38) seals, sampled between 1998 and 2002 from Baltic Sea, Svalbard, and Sable Island (Canada) were used to investigate relationships between PCB exposure and sex hormone concentrations (progesterone; P4, 17α-hydroxy progesterone; 17α-OH-P4, testosterone; T4, 17ß-estradiol; E2, estrone; E3). Immunoassay methods were used for quantification of analytes due to the limited sample volumes available. PCB concentrations were found to be significantly higher in Baltic seals than other sampling locations and were classed as "Exposed" seals while Svalbard and Sable Is seal were classed "Reference" seals (sexes and species separate). Mean hormone concentrations in Exposed seal were lower than Reference seals, and this was statistically significantly for 17α-OH-P4 (both sexes and both species), E2 (ringed and grey seal females), and E3 (grey seal females). Regression analyses (PCB v hormone concentrations) for each sex and species revealed significant correlations for P4 (Sable Is. female grey seals and female ringed seals), 17α-OH-P4 (Sable Is. male grey seals and Svalbard male ringed seals), T4 (Svalbard male ringed seals), E2 (female ringed seals), and E3 (female ringed seals and Baltic female grey seals). Although significant correlations are not evidence of cause and effect, the potential impact of hormone changes on endocrine homeostasis and reproductive health for seal populations warrants further investigation given that PCB concentrations found here are in the same range as those currently reported in seals from these populations.


Assuntos
Disruptores Endócrinos/toxicidade , Hormônios Esteroides Gonadais/sangue , Bifenilos Policlorados/toxicidade , Focas Verdadeiras/sangue , Poluentes Químicos da Água/toxicidade , Animais , Canadá , Disruptores Endócrinos/análise , Feminino , Masculino , Oceanos e Mares , Bifenilos Policlorados/análise , Água do Mar/química , Svalbard , Poluentes Químicos da Água/análise
15.
Artigo em Inglês | MEDLINE | ID: mdl-32075001

RESUMO

Although most countries banned manufacturing of polychlorinated biphenyls (PCBs) over 40 years ago, PCBs remain a global concern for wildlife and human health due to high bioaccumulation and biopersistance. PCB uptake mechanisms have been well studied in many taxa; however, less is known about depuration rates and how post-exposure diet can influence PCB concentrations and immune response in fish and wildlife populations. In a controlled laboratory environment, we investigated the influence of subchronic dietary exposure to two PCB Aroclors and food deprivation on tissue-specific concentrations of total PCBs and PCB homologs and innate immune function in channel catfish (Ictalurus punctatus). Overall, we found that the concentration of total PCBs and PCB homologs measured in whole body, fillet, and liver tissues declined more slowly in food-deprived fish, with slowest depuration observed in the liver. Additionally, fish that were exposed to PCBs had lower plasma cortisol concentrations, reduced phagocytic oxidative burst activity, and lower cytotoxic activity, suggesting that PCBs can influence stress and immune responses. However, for most measures of immune function, the effects of food deprivation had a larger effect on immune response than did PCB exposure. Taken together, these results suggest that short-term dietary exposure to PCBs can increase toxicity of consumable fish tissues for several weeks, and that PCB mixtures modulate immune and stress responses via multiple pathways. These results may inform development of human consumption advisories and can help predict and understand the influence of PCBs on fish health.


Assuntos
Arocloros , Exposição Dietética , Ictaluridae , Imunomodulação , Bifenilos Policlorados , Animais , Arocloros/farmacocinética , Arocloros/toxicidade , Privação de Alimentos , Humanos , Imunomodulação/efeitos dos fármacos , Bifenilos Policlorados/farmacocinética , Bifenilos Policlorados/toxicidade , Distribuição Tecidual
16.
Environ Health ; 19(1): 23, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093744

RESUMO

BACKGROUND: In light of the vulnerability of the developing brain, mixture risk assessment (MRA) for the evaluation of developmental neurotoxicity (DNT) should be implemented, since infants and children are co-exposed to more than one chemical at a time. One possible approach to tackle MRA could be to cluster DNT chemicals in a mixture on the basis of their mode of action (MoA) into 'similar' and 'dissimilar', but still contributing to the same adverse outcome, and anchor DNT assays to common key events (CKEs) identified in DNT-specific adverse outcome pathways (AOPs). Moreover, the use of human in vitro models, such as induced pluripotent stem cell (hiPSC)-derived neuronal and glial cultures would enable mechanistic understanding of chemically-induced adverse effects, avoiding species extrapolation. METHODS: HiPSC-derived neural progenitors differentiated into mixed cultures of neurons and astrocytes were used to assess the effects of acute (3 days) and repeated dose (14 days) treatments with single chemicals and in mixtures belonging to different classes (i.e., lead(II) chloride and methylmercury chloride (heavy metals), chlorpyrifos (pesticide), bisphenol A (organic compound and endocrine disrupter), valproic acid (drug), and PCB138 (persistent organic pollutant and endocrine disrupter), which are associated with cognitive deficits, including learning and memory impairment in children. Selected chemicals were grouped based on their mode of action (MoA) into 'similar' and 'dissimilar' MoA compounds and their effects on synaptogenesis, neurite outgrowth, and brain derived neurotrophic factor (BDNF) protein levels, identified as CKEs in currently available AOPs relevant to DNT, were evaluated by immunocytochemistry and high content imaging analysis. RESULTS: Chemicals working through similar MoA (i.e., alterations of BDNF levels), at non-cytotoxic (IC20/100), very low toxic (IC5), or moderately toxic (IC20) concentrations, induce DNT effects in mixtures, as shown by increased number of neurons, impairment of neurite outgrowth and synaptogenesis (the most sensitive endpoint as confirmed by mathematical modelling) and increase of BDNF levels, to a certain extent reproducing autism-like cellular changes observed in the brain of autistic children. CONCLUSIONS: Our findings suggest that the use of human iPSC-derived mixed neuronal/glial cultures applied to a battery of assays anchored to key events of an AOP network represents a valuable approach to identify mixtures of chemicals with potential to cause learning and memory impairment in children.


Assuntos
Rotas de Resultados Adversos , Poluentes Ambientais/toxicidade , Síndromes Neurotóxicas/etiologia , Neurotoxinas/toxicidade , Disruptores Endócrinos/toxicidade , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Metais Pesados/toxicidade , Células-Tronco Neurais/efeitos dos fármacos , Praguicidas/toxicidade , Bifenilos Policlorados/toxicidade , Medição de Risco , Testes de Toxicidade
17.
Environ Int ; 136: 105433, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918334

RESUMO

BACKGROUND: Experimental evidence has revealed that exposure to polychlorinated biphenyls (PCBs) and dioxins directly impairs endothelial function and induces atherosclerosis progression. In the general population, despite a small number of recent studies finding a link between PCBs, and stroke and myocardial infraction, the association with early coronary atherosclerosis has not been examined yet. OBJECTIVE: To examine whether dietary exposure to PCBs and dioxins is associated with subclinical coronary atherosclerosis in a middle-aged men. DESIGN: Cross-sectional analysis comprising 1844 men in their 50 s and free of cardiovascular disease, who participated in the Aragon Workers' Health Study (AWHS). Individual dietary exposures to PCBs and dioxins were estimated by the contaminant's concentration in food coupled with the corresponding consumption and then participants were classified into quartiles of consumption. Coronary artery calcium score (CACS) was assessed by computerized tomography. We conducted ordered logistic regressions to estimate the odds ratio (OR) and 95% confidence intervals (CIs) for progression to the categories of more coronary artery calcium, adjusting for potential confounders. RESULTS: Among the participants, coronary calcium was not shown in 60.1% (n = 1108), 29.8% had a CACS > 0 and <100 (n = 550), and the remaining 10.1% (n = 186) had a CACS ≥ 100. Compared with those in the first quartile of PCBs exposure, those in the fourth one had an increased odds for having coronary calcium (OR 2.02, 95% CI [1.18, 3.47], p trend 0.019) and for having progressed to categories of more intense calcification (OR 2.03, 95% CI [1.21, 3.40], p trend 0.012). However, no association was found between dietary dioxins exposure and prevalent coronary artery calcium. CONCLUSIONS: In this general male population, dietary exposure to PCBs, but not to dioxins, was associated with a higher prevalence of coronary calcium and to more intense subclinical coronary atherosclerosis. PCBs exposure seems to increase the risk of coronary disease in men from the very early stages.


Assuntos
Doença da Artéria Coronariana , Dieta , Dioxinas , Bifenilos Policlorados , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Dioxinas/toxicidade , Humanos , Masculino , Pessoa de Meia-Idade , Bifenilos Policlorados/toxicidade
18.
Environ Sci Process Impacts ; 22(2): 364-380, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942891

RESUMO

River islands (Ait or Eyot) within the inner tidal Thames serve as unique recorders of current and historical estuarine chemical pollution. Sediment cores from Chiswick Ait were assessed for contamination using Microtox® solid phase bioassay, stable isotopes (δ13C, δ15N), heavy metals and polychlorinated biphenyls (PCBs). Microtox® classified these sediments as non-toxic to moderately toxic and bulk isotopes identified a change in organic input. Metals Cu, Zn, Cr, Ni, Cd, Hg and Ag showed parallel rise, peak and fall profiles which when allied to a 207/208Pb and 137Cs based chronology supported major changes in trace metal contributions corresponding to approximate input times of 1940 (rise), 1963 (peak) and 1985 (fall). Metals ranged from Cu 15 to 373 mg kg-1 (mean 141 mg kg-1), Zn 137 to 1331 mg kg-1 (mean 576 mg kg-1), Cr 14-351 mg kg-1 (mean 156 mg kg-1), Pb 10 to 1506 mg kg-1 (mean 402 mg kg-1), As 1 to 107 (mean 38 mg kg-1), Ni 11 to 113 mg kg-1 (mean 63 mg kg-1), Cd 0.2 to 53 mg kg-1 (mean 9 mg kg-1), Hg 1 to 8 mg kg-1 (mean 4.6 mg kg-1) and Ag from 0.7 to 50 mg kg-1 (mean 7.5 mg kg-1). Down core total PCBs ranged from 10.5 to 121 µg kg-1 and mean of 39 µg kg-1. The rise, peak and fall of Cu, Zn, Cr, Ni, Cd and Ag pollution matched local sewage works' treatment discharge records. Whereas the Hg, Pb and As profiles were disconnected, reflecting alternative historic sources and or partitioning behaviour. Comparison to marine sediment quality guidelines indicate that Zn, Pb, Ni, Cd and Hg exceed action level 2, whereas sedimentary Cu, Cr and As concentrations were above action level 1 (no action) but below action level 2 (further investigation required). The river islands of the tidal Thames capture a unique contaminant chemistry record due in part to their location in the tidal frame (salinity minimum) and close proximity to west London.


Assuntos
Metais Pesados , Bifenilos Policlorados , Poluentes Químicos da Água , China , Monitoramento Ambiental , Estuários , Sedimentos Geológicos , Londres , Metais Pesados/toxicidade , Bifenilos Policlorados/toxicidade , Rios , Poluentes Químicos da Água/toxicidade
19.
Chemosphere ; 246: 125775, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918092

RESUMO

Cancer stem cells (CSCs) are a very small subpopulation that have stem-cell qualities, such as exhibiting self-renewal, immortality, and pluripotency, and the capability to differentiate into different tumor cell subtypes. CSCs contribute to tumor onset, expansion, metastasis, resistance and recurrence. Meanwhile, organic pollutants, including nonpersistent pollutants, such as bisphenol A (BPA), and persistent pollutants, such as polychlorinated biphenyls (PCBs), are toxic chemicals that can be readily ingested via dietary exposure and other exposure routes and can accumulate through the food chain. Many organic pollutants increase the risk of ovarian cancer depending on their estrogenic effects. Nonetheless, most previous studies have focused on the toxic effects of these pollutants on the proliferation, metastasis and development of ovarian cancer cells. However, little research has investigated the adverse effect of these pollutants on ovarian cancer stem cells. The current study found that BPA, PCB126 and PCB153 greatly enhanced the formation of cancer stem-like cell spheres of OVCAR-3 cells (human ovarian cancer cells) under low-dose exposure. In parallel, the CD44highCD24low cell subpopulation was increased in treated cells relative to untreated cells. Elevated expression of cancer stem cell markers, including ALDH1A1, CD133, SOX2, NANOG and OCT4, was demonstrated in treated cells compared to untreated cells. In summary, these data demonstrate that the oncogenic effects of pollutants can be evaluated according to changes in caner stem cell properties.


Assuntos
Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Bifenilos Policlorados/toxicidade , Via de Sinalização Wnt/fisiologia , Apoptose , Linhagem Celular Tumoral , Feminino , Humanos , Receptores de Hialuronatos , Células-Tronco Neoplásicas , Neoplasias Ovarianas/metabolismo , Bifenilos Policlorados/metabolismo , Testes de Toxicidade , Via de Sinalização Wnt/efeitos dos fármacos
20.
Aquat Toxicol ; 220: 105397, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954981

RESUMO

Within monitoring frameworks, biomarkers provide several benefits because they serve as intermediates between pollutant exposure and effects, and integrate the responses of contaminants that operate through the same mechanism of action. This study was designed to verify the use of transcriptomic biomarkers developed in our prior work (i.e., Coastal Biosensor of Endocrine Disruption; C-BED assay) on Mytilus edulis and identify additional biomarkers for legacy pollutants. M. edulis were collected from a reference site in Pemaquid, ME, USA and deployed by the Massachusetts Water Resources Authority (MWRA) at locations in and outside Boston Harbor, MA, USA: including (1) Boston Inner Harbor (IH), (2) the current outfall (OS), (3) 1 km away from the current outfall (LNB), and (4) Deer Island (DI), the site where untreated wastewater was formerly discharged into the bay. Differential gene expression was quantified with a high density microarray. Seven genes significantly correlated with whole tissue concentration of PAHs, and six genes significantly correlated with whole body concentrations of PCBs, two groups of legacy contaminants that were elevated at stations IH, OS, and DI. Enrichment analysis indicated that IH mussels had the highest induction of stress response genes, which correlated with the higher levels of contaminants measured at this site. Based on the C-BED assay gene analysis, stations IH and OS exhibited signs of endocrine disruption, which were further confirmed by incorporating the results for the C-BED assay within the Integrated Biomarker Response (IBR) approach. This study successfully demonstrated the potential use of transcriptomic biomarkers within a monitoring program to identify the presence and organismal responses to endocrine disrupting and legacy contaminant classes.


Assuntos
Disruptores Endócrinos/toxicidade , Biomarcadores Ambientais/genética , Monitoramento Ambiental/métodos , Mytilus edulis/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Disruptores Endócrinos/análise , Mytilus edulis/genética , New England , Bifenilos Policlorados/análise , Bifenilos Policlorados/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Água do Mar/química , Poluentes Químicos da Água/análise
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