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1.
Chemosphere ; 263: 128086, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297084

RESUMO

Polychlorinated dioxins and dibenzofurans (PCDD/Fs) are highly toxic contaminants that are strictly regulated and monitored in the environment and food to reduce human exposure. Recently, the increasing occurrence of polybrominated dioxins and dibenzofurans (PBDD/Fs) in the environment is raising concerns about the impact on human health by the combined exposure to chlorinated and brominated analogues of dioxins. Toxicological properties of PBDD/Fs relative to PCDD/Fs have not been firmly established, and brominated dioxins are not included in routine monitoring programs. In this study, we set out to determine human-relevant congener-specific potency values for a range of brominated and chlorinated dioxin congeners, based on their aryl hydrocarbon receptor (AhR)-mediated mode of toxic action. Transactivation of the AhR was measured using dioxin-responsive (DR) CALUX reporter gene assays. Because of known species-differences in dioxin-mediated toxicity, we developed and used a HepG2 human liver cell-based DR human CALUX assay that is a variant of the rodent-based DR CALUX. The assay was found to be highly inducible and stable, with low variations between independent measurements. Using both DR CALUX assays in an automated high-throughput mode we found that overall PBDD/Fs were as potent as PCDD/Fs in inducing AhR transactivation, but congener-specific differences were observed. We also observed species-specific differences in sensitivity and potency when comparing DR human REP values to those obtained in the rat-based DR CALUX. Finally, we observed significant differences between WHO-TEF values and DR human REP values, suggesting that actual WHO-TEF values may underestimate the hazards associated with exposure of humans to dioxins.


Assuntos
Dioxinas , Dibenzodioxinas Policloradas , Animais , Dibenzofuranos , Dibenzofuranos Policlorados , Dioxinas/toxicidade , Genes Reporter , Humanos , Dibenzodioxinas Policloradas/toxicidade , Ratos , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Ativação Transcricional
2.
Bull Environ Contam Toxicol ; 105(1): 173-179, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32632464

RESUMO

In order to assess environmental exposure-associated human health risk of dioxin compounds for the population in the vicinity of a municipal solid waste incinerator (MSWI) in Shanghai, the atmospheric samples (n = 24) and soils samples (n = 96) were collected and analyzed to obtain the concentration level, pollution characteristics and seasonal changes of dioxin compounds in environmental medias. The toxicity equivalent concentration range of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) was 30.9-409 fg WHO-TEQ·m-3 in atmosphere and 0.362-8.55 ng WHO-TEQ·kg-1 in soil. The non-carcinogenic health risk and carcinogenic health risk from PCDD/Fs environmental exposure of people living in the vicinity of the MSWI in Shanghai were all within the allowable range of the US Environmental Protection Agency, which implied that the MSWI in Shanghai did not produce additional risk for the population living in its vicinity.


Assuntos
Poluentes Atmosféricos/análise , Dioxinas/toxicidade , Exposição Ambiental , Incineração , Poluentes Atmosféricos/toxicidade , Atmosfera , China , Dibenzofuranos , Dibenzofuranos Policlorados/análise , Dioxinas/análise , Monitoramento Ambiental , Humanos , Dibenzodioxinas Policloradas/análise , Solo , Resíduos Sólidos/análise
3.
Environ Int ; 143: 105984, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32712422

RESUMO

Dioxins, a group of persistent organic pollutants, have been proved to correlate with ranges of diseases by activating the aryl hydrocarbon receptor (AhR). However, previous dioxin toxicity studies primarily focused on the activation of AhR with signaling pathways at gene and protein levels. The investigation of underlying mechanisms at the metabolic level is still necessary. In this study, serum samples of 48 and 47 healthy participants with the highest and lowest dioxin levels based on quartile distribution of the serum dioxin concentrations of 215 male adults were selected for metabolomics analysis by using liquid chromatography coupled with orbitrap high-resolution mass spectrometry to investigate dioxin-related metabolic responses. The identified potential biomarkers included acylcarnitines, fatty acids and derivatives, glycerophospholipids, etc. suggested that metabolic pathways such as fatty acid ß-oxidation, essential fatty acid metabolism, arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolism and purine metabolism were disturbed by dioxin exposure. The results indicated that people with high dioxin exposure levels were at the potential health risks of inflammation, liver and cardiovascular diseases. The metabolic findings may help understand the link between dioxin exposure and the diseases.


Assuntos
Dioxinas , Dibenzodioxinas Policloradas , Grupo com Ancestrais do Continente Asiático , Dioxinas/toxicidade , Humanos , Fígado , Masculino , Metabolômica , Receptores de Hidrocarboneto Arílico
4.
Environ Res ; 183: 109280, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32311913

RESUMO

BACKGROUND: In animal studies, perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters thyroid homoeostasis and thyroid hormone concentrations; epidemiologic evidence is limited. OBJECTIVES: We aimed to determine the association of prenatal exposure to TCDD with thyroid hormone concentrations in the Seveso Second Generation Study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 chemical factory explosion in Seveso, Italy. METHODS: We included 570 children (288 female, 282 male) with complete follow-up data, including a fasting blood draw. Serum levels of total and free thyroxine (T4), free triiodothyronine (T3), and thyroid stimulating hormone (TSH) were measured using immunoassays. We defined prenatal TCDD exposure as: 1) maternal initial TCDD concentration measured in serum collected soon after the explosion and 2) maternal TCDD estimated at pregnancy. RESULTS: Compared to the lowest quartile (Q1), maternal initial serum TCDD was associated with lower free T3 (Q2: adj-ß = -0.13, 95%CI -0.26, 0.00; Q3: adj-ß = -0.22, 95%CI -0.35, -0.09; Q4: adj-ß = -0.14, 95%CI -0.28, 0.00; p-trend = 0.02). In participants with high thyroid antibody status, inverse associations between maternal initial serum TCDD and free T3 were significantly stronger than in participants with normal antibody status (p-interaction = 0.02). We also observed a positive association between maternal initial serum TCDD and TSH concentrations in participants with high thyroid antibody status (Q2: adj-ß = 11.4%, 95%CI -25.2, 66.1; Q3: adj-ß = 49.0%, 95%CI 3.0, 115.5; Q4: adj-ß = 105.5, 95%CI 36.6, 209.2; p-trend < 0.01) but not in those participants with normal antibody status (p-interaction < 0.01). Similar results were found for TCDD estimated at pregnancy. DISCUSSION: Our results suggest prenatal exposure to TCDD, a potent endocrine-disrupting compound, may alter thyroid function later in life. Populations with additional thyroid stress may be particularly susceptible to in utero exposure of thyroid disrupting chemicals.


Assuntos
Dioxinas , Efeitos Tardios da Exposição Pré-Natal , Glândula Tireoide , Hormônios Tireóideos , Animais , Anticorpos , Criança , Dioxinas/toxicidade , Feminino , Humanos , Itália , Masculino , Dibenzodioxinas Policloradas , Gravidez , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/imunologia , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/metabolismo
5.
Int J Mol Sci ; 21(7)2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32231017

RESUMO

Dioxins and related compounds are common environmental contaminants. Although their levels have gone down, they are still of concern, in particular regarding developmental toxicity. The adverse effects of these compounds are mediated by the aryl hydrocarbon receptor (AHR), whose canonical signaling pathway has been unveiled in fair detail. The alternative (non-genomic) pathways are much more obscure. AHR has also proven to be a master regulator of numerous physiological phenomena, which has led to the search of selective AHR modulators with low toxicity. Papers of this Special Issue address the developmental toxicity of dioxins and related compounds as well as selective modulators of AHR and both its canonical and alternative signaling pathways. In addition, new optical and stereoscopic methods for the detection of dioxins are presented. As a whole, this Special Issue provides an up-to-date view on a wide variety of aspects related to dioxin toxicity mechanisms from both original research articles and reviews.


Assuntos
Dioxinas/toxicidade , Poluentes Ambientais/toxicidade , Animais , Dioxinas/química , Poluentes Ambientais/química , Humanos , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Environ Res ; 186: 109516, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32305677

RESUMO

BACKGROUND: Dioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed. OBJECTIVES: To prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses' Health Study II (NHSII). METHODS: NHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: From 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status. DISCUSSION: Results from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk.


Assuntos
Neoplasias da Mama , Dioxinas , Dibenzodioxinas Policloradas , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Dioxinas/toxicidade , Feminino , Humanos , Estudos Prospectivos , Risco
7.
Environ Int ; 139: 105731, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32315892

RESUMO

Electrical and electronic waste (e-waste) burning and recycling activities have become one of the main emission sources of dioxin-like compounds (DLCs). Workers involved in e-waste recycling operations and residents living near e-waste recycling sites (EWRS) are exposed to high levels of DLCs. Epidemiological and experimental in vivo studies have reported a range of interconnected responses in multiple systems with DLC exposure. However, due to the compositional complexity of DLCs and difficulties in assessing mixture effects of the complex mixture of e-waste-related contaminants, there are few studies concerning human health outcomes related to DLC exposure at informal EWRS. In this paper, we have reviewed the environmental levels and body burdens of DLCs at EWRS and compared them with the levels reported to be associated with observable adverse effects to assess the health risks of DLC exposure at EWRS. In general, DLC concentrations at EWRS of many countries have been decreasing in recent years due to stricter regulations on e-waste recycling activities, but the contamination status is still severe. Comparison with available data from industrial sites and well-known highly DLC contaminated areas shows that high levels of DLCs derived from crude e-waste recycling processes lead to elevated body burdens. The DLC levels in human blood and breast milk at EWRS are higher than those reported in some epidemiological studies that are related to various health impacts. The estimated total daily intakes of DLCs for people in EWRS far exceed the WHO recommended total daily intake limit. It can be inferred that people living in EWRS with high DLC contamination have higher health risks. Therefore, more well-designed epidemiological studies are urgently needed to focus on the health effects of DLC pollution in EWRS. Continuous monitoring of the temporal trends of DLC levels in EWRS after actions is of highest importance.


Assuntos
Dioxinas , Resíduo Eletrônico , Carga Corporal (Radioterapia) , Dioxinas/análise , Dioxinas/toxicidade , Feminino , Humanos , Leite Humano/química , Reciclagem
8.
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
9.
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
10.
Chemosphere ; 244: 125448, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31812059

RESUMO

Here, we characterized the dioxin-like activities of 42 polychlorinated naphthalenes (PCNs) and 6 technical Halowax formulations by using the DR-CALUX (dioxin-responsive chemically activated luciferase expression) assay with rat hepatoma luciferase-expressing H4IIE cells. Of the 42 PCNs examined, 31 showed dioxin-like activities, for which the mass-based REP-EC5TCDD (potency relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin based on the 5% effective concentration determined from the dose-response curve for 2,3,7,8-TCDD) ranged from 0.00000012 to 0.0051, indicating that some of the PCNs (e.g., 1,2,3,6,7,8-HxCN and 1,2,3,4,6,7-HxCN) had dioxin-like activities that were equal to or higher than the WHO-TEFs and the mass-based REP-EC5TCDD reported for dioxins such as octachlorodibenzo-p-dioxin, octachlorodibenzofuran, 3,3',4,4'-tetrachlorobiphenyl (PCB-77), 3,4,4',5-tetrachlorobiphenyl (PCB-81), and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB-169). For PeCNs to OCN with high dioxin-like activities, REPs determined in previous studies were comparable to the REP values obtained in the present study. The TCDD-EQs (2,3,7,8-TCDD equivalents) obtained experimentally for the Halowax formulations decreased in the order HW1051 (37 mg/kg) > HW1014 (30 mg/kg) > HW1013 (5.6 mg/kg) > HW1099 (2.9 mg/kg) > HW1001 (0.60 mg/kg) > HW1031 (<0.10 mg/kg) and were comparable to the theoretical TCDD-EQs calculated by multiplying the concentration and REP of each PCN. In addition, the theoretical TCDD-EQs for PCNs in emission gases produced by thermal processes were below the Japanese emission standard of 0.1-10 ng WHO-toxicity equivalent (TEQ)/m3N, and 3 to 4 orders of magnitude lower than the corresponding WHO-TEQ. Based on a comparison of theoretical and experimental TCDD-EQs, we found that our REP-based approach was suitable for the risk management of industrially produced and unintentionally generated dioxin-like PCNs. This approach will be particularly useful for the risk management of unintentionally generated PCNs in emission gases because the contribution of dioxin-like PCNs to the whole dioxin-like toxicity of emission gases can be elucidated.


Assuntos
Dioxinas/toxicidade , Poluentes Ambientais/toxicidade , Naftalenos/toxicidade , Animais , Benzofuranos , Bioensaio , Luciferases/metabolismo , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Ratos , Gestão de Riscos , Testes de Toxicidade
11.
Environ Pollut ; 255(Pt 3): 113357, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31671369

RESUMO

Gut microbiota is of critical importance to host health. Aryl hydrocarbon receptor (AhR) is found to be closely involved in the regulation of gut microbial dynamics. However, it is still not clear how AhR signaling shapes the gut microbiota. In the present study, adult zebrafish were acutely exposed to an AhR antagonist (CH223191), an AhR agonist (polychlorinated biphenyl 126; PCB126) or their combination for 7 d. Overall intestinal health and gut microbial community were temporally monitored (1 d, 3 d and 7 d) and inter-compared among different groups. The results showed that single exposure to PCB126 significantly disrupted the overall health of intestines (i.e., neural signaling, inflammation, epithelial barrier integrity, oxidative stress). However, CH223191 failed to inhibit but enhanced the physiological toxicities of PCB126, implying the involvement of extra mechanisms rather than AhR in the regulation of intestinal physiological activities. Dysbiosis of gut microbiota was also caused by PCB126 over time as a function of sex. It is intriguing that CH223191 successfully abolished the holistic effects of dioxin on gut microbiota, which inferred that growth of gut microbes was directly controlled by AhR activation without the involvement of host feedback modulation. When coming to detailed alterations at certain taxon, both antagonistic and synergistic interactions existed between CH223191 and dioxin, depending on fish sex, exposure duration and bacterial species. Correlation analysis found that gut inflammation was positively associated with pathogenic Legionella bacteria, but was negatively associated with epithelial barrier integrity, suggesting that integral intestinal epithelial barrier can prevent the influx of pathogenic bacteria to induce inflammatory response. Overall, this study has deciphered, for the first time, the direct regulative effects of AhR activity on gut microbiota. Future research is warranted to elucidate the specific mechanisms of AhR action on certain bacterial population.


Assuntos
Dioxinas/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Bactérias/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Disbiose , Intestinos , Microbiota , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Peixe-Zebra/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-31671717

RESUMO

In the United States, more than 200 communities are designated by the U.S. Environmental Protection Agency as areas of concern for dioxins. Informing the public about potential risks associated with dioxins and delivering information about how to avoid such risks are essential activities. News coverage of environmental and health problems affects how members of the public assess those problems in terms of both severity and how they are understood, as well as the extent of attention given to the problem by policy-makers. To contextualize public and institutional responses to dioxin contamination and remediation in a dioxin-affected community, we assessed 176 newspaper articles published over 30 years concerning dioxin contamination in Midland, Michigan, in terms of risk, trust in institutions, environmental stigma, and citizen participation. Articles about dioxin contamination and remediation in Midland appeared in both domestic and international newspapers. Domestically, both national and local newspapers covered this issue. The risks for human health and the environment caused by exposure to dioxins were widely covered, with much less media attention given to the trustworthiness of the organizations responsible for managing the risk, environmental stigma, and citizen participation. News coverage of these four themes also changed significantly overtime. Overall, our findings highlight the important role of local news media in communicating risk information, guiding safe behaviors, and facilitating community-level decision-making.


Assuntos
Dioxinas , Poluentes Ambientais , Poluição Ambiental , Meios de Comunicação de Massa , Jornais como Assunto , Atitude Frente a Saúde , Participação da Comunidade , Dioxinas/análise , Dioxinas/toxicidade , Saúde Ambiental , Política Ambiental , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Poluição Ambiental/efeitos adversos , Poluição Ambiental/análise , Poluição Ambiental/prevenção & controle , Poluição Ambiental/estatística & dados numéricos , Humanos , Meios de Comunicação de Massa/estatística & dados numéricos , Michigan , Jornais como Assunto/estatística & dados numéricos , Risco , Estigma Social , Confiança
13.
Andrologia ; 51(11): e13411, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31599008

RESUMO

The CatSper gene family is known to be solely expressed in sperm cells and is possibly associated with sperm motility and penetration through the zona pellucida. Despite its vital role in male fertility, factors regulating its expression are not widely known. The present study aimed at evaluating the effects of dioxin on CatSper2 gene and protein expression, testicular histopathology, sperm quality and biochemical parameters in a mice model. The experiments were performed on 32 Naval Medical Research Institute male mice (2-3 months). The animals were divided into four groups in a random manner: (a) control; (b) dioxin 1; (c) dioxin 2; and (d) dioxin 3. The treatment groups received 0.1, 0.5 and 1 µg/kg of dioxin intraperitoneally every day for 2 weeks. Administration of dioxin significantly downregulated the CatSper2 gene and protein expression. A greater reduction in gene and protein expression was found at higher doses of dioxin. At the same time, sperm parameters, especially sperm motility and count, decreased in mice exposed to dioxin. The results of testicular histopathology showed necrotic degeneration and epithelium thickness reduction in the dioxin groups in comparison with the controls. Besides, oxidative stress increased in seminiferous tubules.


Assuntos
Canais de Cálcio/metabolismo , Dioxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Canais de Cálcio/genética , Masculino , Camundongos , Distribuição Aleatória , Testículo/patologia
14.
Food Chem Toxicol ; 134: 110803, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563530

RESUMO

Polychlorinated biphenyls (PCBs) would do serious damage to multiple systems, while coplanar polychlorinated biphenyls, the most toxic member of the family, has been widely taken into consideration. In this study, ICR mice were fed with different doses of PCB126 to explore the underlying molecular mechanisms on immunotoxicity. The results showed that PCB126 caused immunosuppression as evidenced by inhibiting the ratios of thymus and spleen weights, changing the organizational structure and decreasing levels and mRNA expression of TNF-α, IFN-γ and IL-2. PCB126 inhibited the SOD activity and spurred the accumulation of MDA in spleen and thymus. Meanwhile, it also disturbed the Nrf2 signaling pathway as evidenced by up-regulating the mRNA expression of Nrf2 and Keap1. Additionally, a remarkable reduction in the mRNA expression of AhR and enhancement in the mRNA expression of Cyp1 enzymes (Cyp1a1, Cyp1a2 and Cyp1b1) were observed, which increased the ROS levels. PCB126 could increase protein expression of Bax, Caspase-3, Caspase-8 and Caspase-9, while the protein expression of Bcl-2 was decreased. In summary, the results indicated that PCB126 modulated the AhR signaling pathway, which interacted with apoptosis and oxidative stress to induce immunotoxicity, enrich the immunotoxicological mechanisms of PCB126.


Assuntos
Apoptose/efeitos dos fármacos , Dioxinas/toxicidade , Mitocôndrias/metabolismo , Bifenilos Policlorados/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Baço/efeitos dos fármacos , Baço/imunologia , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Feminino , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Baço/citologia , Baço/enzimologia , Superóxido Dismutase-1/metabolismo , Timo/efeitos dos fármacos , Timo/enzimologia , Timo/metabolismo
15.
Hum Exp Toxicol ; 38(9): 1014-1023, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31169026

RESUMO

Cleft lip and cleft palate also known as orofacial cleft is a congenital malformation involving the partial or total lack of anatomical continuity of craniofacial tissue. The most common environmental factors that may cause orofacial clefts include pharmaceuticals, alcohol, addictive drugs, and tobacco smoke. Living in the area of industrial factories, garbage, ironworks, crematoria, wastewater treatment plants, and plastic waste landfills also has a significant impact on the development of the craniofacial defects. Some of the main factors causing the formation of congenital craniofacial defects are dioxins, of which emission to the environment is an important environmental and health problem. Dioxins are a diverse group of organic chemical compounds, derivatives of oxanthrene and fumarates, which are organoleptically imperceptible. Acting mainly through induction of inflammation, they influence a number of metabolic processes, including the process of bone mineralization and embryonic development. In this work, we highlight the problem of orofacial cleft including the impact of dioxin on development of this defect and the recommended prevention.


Assuntos
Fenda Labial/etiologia , Fissura Palatina/etiologia , Dioxinas/toxicidade , Poluentes Ambientais/toxicidade , Fenda Labial/prevenção & controle , Fissura Palatina/prevenção & controle , Feminino , Humanos , Gravidez
16.
Artigo em Inglês | MEDLINE | ID: mdl-31200452

RESUMO

Polychlorinated biphenyls (PCBs) are well known carcinogenic persistent environmental pollutants and endocrine disruptors. Our aim was to identify the possible dysregulation of genes in PCB exposed peripheral blood mononuclear cells (PBMCs) in order to give more insight into the differential pathophysiological effects of PCB congeners and mixtures, with an emphasis on immunological effects and oxidative stress. The PBMCs of a healthy volunteer (male, 56 years old) were exposed to a mixture of dioxin-like (DL)-PCBs (PCB 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189, 250 µg/L resp.) or non-dioxin-like (NDL)-PCBs (PCB 28, 52, 101, 138, 153, 180, 250 µg/L resp.) or single PCB congener (no.28, 138, 153, 180, 250 µg/L resp.). After an incubation period of 24 h, a microarray gene expression screening was performed, and the results were compared to gene expression in control samples (PBMCs treated with the vehicle iso-octane). Treatment of PBMCs with the DL-PCB mixture resulted in the largest number of differentially regulated genes (181 upregulated genes >2-fold, 173 downregulated >2-fold). Treatment with the NDL-PCB mix resulted in 32 upregulated genes >2-fold and 12 downregulated genes >2-fold. A gene set enrichment analysis (GSEA) on DL-PCB treated PBMCs resulted in an upregulation of 125 gene sets and a downregulation of 76 gene sets. Predominantly downregulated gene sets were involved in immunological pathways (such as response to virus, innate immune response, defense response). An upregulation of pathways related to oxidative stress could be observed for all PCB congeners except PCB-28; the latter congener dysregulated the least number of genes. Our experiment augments the information known about immunological and cellular stress responses following DL- as well as NDL-PCB exposure and provides new information on PCB 28. Further studies should be performed to evaluate how disruption of these pathways contributes to the development of autoimmune diseases and cancer.


Assuntos
Carcinógenos/toxicidade , Dioxinas/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Expressão Gênica/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Células Cultivadas , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade
17.
Chem Biol Interact ; 308: 51-60, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31085170

RESUMO

Chrysin belongs to the flavonoids and has been used as traditional medicine from ancient and has been reported to exhibit a wide range of pharmacological properties. The biochemical and molecular mechanisms involved in the hepato- and nephroprotective activities of chrysin were discussed in this review. Chrysin exhibited hepatoprotective activity against 2,3,7,8-tetrachlorodibenzo-p-dioxin, carbon tetrachloride, cisplatin, d-galactosamine, doxorubicin, ethanol, lipopolysaccharide/d-galactosamine, methotrexate, ammonium chloride, paracetamol, diethylnitrosamine, streptozotocin, tert-butyl hydroperoxide, thioacetamide, 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), ischemia/reperfusion-induced hepatotoxicity and nephroprotective activity against cisplatin, doxorubicin, paracetamol, gentamicin, streptazotocin, N-nitrosodiethyl amine, 5-fluorouracil, adenine, carbon tetrachloride, copper, 2,3,7,8-tetrachlorodibenzo- p-dioxin, colistin, Nω-nitro-l-arginine-methylester and ethanol in various animal models due to its antioxidant, anti-apoptotic activities. In this review, we provide an overview of the possible mechanisms by which chrysin reduced the hepatotoxicity and nephrotoxicity of different toxicants. This will help the toxicologists, pharmacologists and chemists to develop new safer pharmaceutical products with chrysin and other toxicants.


Assuntos
Flavonoides/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Dioxinas/toxicidade , Flavonoides/química , Flavonoides/uso terapêutico , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico
18.
Environ Sci Pollut Res Int ; 26(20): 20780-20786, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102233

RESUMO

The purpose of this study was to investigate the longitudinal effects of perinatal exposure to dioxin on physical growth in a 3-year follow-up study. In 2015, 27 mother-infant pairs living in an electronic waste (e-waste) dismantling region and 35 pairs living in a control region were enrolled in the present study. Breast milk samples were collected at 4 weeks after birth. Physical growth, including weight, height, and head and chest circumferences, was measured at 6 months and 3 years of age. Dioxin levels in the breast milk were measured by gas chromatography/high-resolution mass spectrometry. Levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and toxic equivalency values in maternal breast milk of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and PCDDs/PCDFs were significantly higher in women residing in the e-waste dismantling region. In 3-year-old boys, inverse associations were found between height and PCDDs-TEQ. In girls, positive associations were found between height and 2,3,7,8-TetraCDD, PCDDs-TEQ, and PCDDs/PCDFs-TEQ, and for weight and PCDDs-TEQ and PCDDs/PCDFs-TEQ at 3 years of age. In this study, sex-specific differences were observed in children, in whom dioxin exposure decreased growth in boys but increased growth in girls during the first 3 years of life.


Assuntos
Dioxinas/análise , Dioxinas/toxicidade , Resíduo Eletrônico/efeitos adversos , Exposição Ambiental/efeitos adversos , Leite Humano/química , Adulto , Tamanho Corporal , Aleitamento Materno , Pré-Escolar , China , Estudos de Coortes , Dibenzofuranos Policlorados/análise , Dibenzofuranos Policlorados/toxicidade , Exposição Ambiental/análise , Feminino , Seguimentos , Humanos , Lactente , Estudos Longitudinais , Masculino , Bifenilos Policlorados/análise , Bifenilos Policlorados/toxicidade , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal
19.
Sci Total Environ ; 667: 718-729, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30849612

RESUMO

We previously reported the adverse effects of perinatal dioxin exposure on child neurodevelopment around a former US military airbase in Vietnam. In the present study, we investigated the effects of maternal dioxin exposure on fetal brain development, which may predict neurodevelopmental outcomes in early childhood. A total of 55 newborns with mothers from dioxin-contaminated areas were recruited in the prefecture hospital in Bien Hoa, Vietnam. Dioxins in maternal breast milk collected 1 month after birth were used as a maternal exposure marker. Relative powers and coherence were computed from neonatal electroencephalogram (EEG) records during active sleep stages. Relationships between the EEG parameters and dioxin exposure markers were analyzed using linear regression and a general linear model after adjusting for gestational age, body length, and head circumference of infants at birth. Using data from 47 infants whose neurodevelopment was examined in a 2-year follow-up study, associations between EEG parameters and neurodevelopment were analyzed after adjusting for confounding factors. On the right frontal and parietal regions, relative delta powers were significantly decreased, and relative alpha and beta powers were significantly increased with increasing dioxin exposure. Increases in delta power and decreases in alpha power on the right frontal and parietal regions were associated with an increase in language scores at 2 years of age. Furthermore, intra- and inter-hemispheric coherence in theta and alpha bands were positively and inversely correlated with dioxin exposure, respectively, and increased intra-coherence in the right hemisphere was associated with lower language scores. These findings suggest that prenatal dioxin exposure affects neuronal activity and functional connectivity between brain regions, and may lead to poor language development.


Assuntos
Dioxinas/toxicidade , Poluentes Ambientais/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Exposição Materna/estatística & dados numéricos , Encéfalo , Criança , Pré-Escolar , Dioxinas/metabolismo , Eletroencefalografia , Poluentes Ambientais/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Vietnã
20.
Environ Int ; 124: 236-248, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30658268

RESUMO

BACKGROUND: Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways. OBJECTIVES: We estimated breast cancer risk associated with airborne dioxin exposure, using geographic information system (GIS) methods and historical exposure data. METHODS: We designed a case-control study (429 breast cancer cases diagnosed between 1990 and 2008, matched to 716 controls) nested within the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort. Airborne dioxin exposure was assessed using a GIS-based metric including participants' residential history, technical characteristics of 222 dioxin sources, residential proximity to dioxin sources, exposure duration and wind direction. Odds ratios (OR) and 95% confidence intervals (CI) associated with quintiles of cumulative exposure were estimated using multivariate logistic regression models. RESULTS: We observed no increased risk of breast cancer for higher dioxin exposure levels overall and according to hormone-receptor status. We however observed a statistically significant OR for Q2 versus Q1 overall (1.612, 95% CI: 1.042-2.493) and for estrogen-receptor (ER) positive breast cancer (1.843, 95% CI: 1.033-3.292). CONCLUSIONS: Overall, as well as according to hormone-receptor status, no increased risk was observed for higher airborne dioxin exposure. The increased risk for low exposure levels might be compatible with non-monotonic dose-response relationship. Confirmation of our findings is required. Our GIS-based metric may provide an alternative in absence of ambient dioxin monitoring and may allow assessing exposure to other pollutants.


Assuntos
Poluentes Atmosféricos/toxicidade , Neoplasias da Mama/etiologia , Carcinógenos/toxicidade , Dioxinas/toxicidade , Exposição Ambiental , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Receptor alfa de Estrogênio/metabolismo , Feminino , França , Sistemas de Informação Geográfica , Humanos , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Medição de Risco
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