RESUMO
Polychlorinated biphenyls (PCBs) are synthetic organic contaminants that are widespread in the environment. There are 209 PCB congeners. Fish oil produced from marine fish is widely used as a health supplement. PCB contamination of fish oil is of concern. We determined the concentrations of all 209 PCB congeners in commercially available fish oil supplements from Japan and estimated PCB intakes for humans consuming the supplements. We determined the concentrations of non-dioxin-like PCBs separately. The total PCB concentrations in 37 fish oil supplements purchased in Japan were 0.024-19 ng/g whole weight, and the non-dioxin-like PCB concentration range was also 0.024-19 ng/g whole weight. The total PCB intakes calculated for a 50 kg human consuming the supplements were 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)) and the non-dioxin-like PCB intake range was also 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)). The total PCB intakes were much lower than the tolerable daily intake of 20 ng/(kg body weight per day) recommended by the WHO. The results indicated that PCBs in the fish oil supplements pose acceptable risks to humans consuming the fish oil supplements daily.
Assuntos
Bifenilos Policlorados , Humanos , Bifenilos Policlorados/análise , Óleos de Peixe , Japão , Suplementos Nutricionais/análise , Peso Corporal , Contaminação de Alimentos/análiseRESUMO
The regeneration of wastewater has been recognized as an effective strategy to counter water scarcity. Nonetheless, Wastewater Treatment Plant (WWTP) effluents still contain a wide range of contaminants of emerging concern (CECs) even after water depuration. Filtration through Soil Aquifer Treatment (SAT) systems has proven efficient for CECs removal although the attenuation of their associated biological effects still remains poorly understood. To evaluate this, three pilot SAT systems were monitored, two of them enhanced with different reactive barriers. SATs were fed with secondary effluents during two consecutive campaigns. Fifteen water samples were collected from the WWTP effluent, below the barriers and 15 m into the aquifer. The potential attenuation of effluent-associated biological effects by SATs was evaluated through toxicogenomic bioassays using zebrafish eleutheroembryos and human hepatic cells. Transcriptomic analyses revealed a wide range of toxic activities exerted by the WWTP effluents that were reduced by more than 70% by SAT. Similar results were observed when HepG2 hepatic cells were tested for cytotoxic and dioxin-like responses. Toxicity reduction appeared partially determined by the barrier composition and/or SAT managing and correlated with CECs removal. SAT appears as a promising approach to efficiently reduce effluent-associated toxicity contributing to environmental and human health preservation.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , Purificação da Água , Animais , Humanos , Peixe-Zebra , Solo , Poluentes Químicos da Água/análise , Água/análise , Monitoramento Ambiental , Eliminação de Resíduos LíquidosRESUMO
Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes developmental and reproductive disorders in pups due to the attenuated luteinizing hormone (LH) production during the perinatal stage; however, the administration of α-lipoic acid (LA) to TCDD-exposed pregnant rats reversed the attenuated LH production. Therefore, reproductive disorders in pups are expected to be ameliorated with LA supplementation. To address this issue, pregnant rats orally received low dose TCDD at gestational day 15 (GD15) and proceeded to parturition. The control received a corn oil vehicle. To examine the preventive effects of LA, supplementation with LA was provided until postnatal day 21. In this study, we demonstrated that maternal administration of LA restored the sexually dimorphic behavior of male and female offspring. TCDD-induced LA insufficiency is likely a direct cause of TCDD reproductive toxicity. In the analysis to clarify the mechanism of the decrease in LA, we found evidence suggesting that TCDD inhibits the synthesis and increases the utilization of S-adenosylmethionine (SAM), a cofactor for LA synthesis, resulting in a decrease in the SAM level. Furthermore, folate metabolism, which is involved in SAM synthesis, is disrupted by TCDD, which may adversely affect infant growth. Maternal supplementation of LA restored SAM to its original level in the fetal hypothalamus; in turn, SAM ameliorated abnormal folate consumption and suppressed aryl hydrocarbon receptor activation induced by TCDD. The study demonstrates that the application of LA could prevent and recover next-generation dioxin reproductive toxicity, which provides the potential to establish effective protective measures against dioxin toxicity.
Assuntos
Ácido Fólico , Exposição Materna , Dibenzodioxinas Policloradas , Efeitos Tardios da Exposição Pré-Natal , Caracteres Sexuais , Desenvolvimento Sexual , Ácido Tióctico , Animais , Feminino , Masculino , Gravidez , Ratos , Feto/efeitos dos fármacos , Feto/metabolismo , Ácido Fólico/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Exposição Materna/efeitos adversos , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , S-Adenosilmetionina/metabolismo , Desenvolvimento Sexual/efeitos dos fármacos , Ácido Tióctico/administração & dosagem , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico , Reprodução/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Meyer (ginseng) is a widely used traditional Chinese medicine that has played a beneficial role in the treatment of various diseases, including liver diseases. Ginsenoside Rg1 is a saponin isolated and purified from ginseng that exerts protective effects on the liver in some liver injury models. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous dioxin found mostly in food products that causes liver injury and other human diseases. Although significant efforts have been made to reduce the burden of liver disease, there is still a lack of effective treatment methods. AIM OF THE STUDY: Although ginsenoside Rg1 was reported to inhibit TCDD-mediated cytochrome P450 1A1 (CYP1A1) induction in HepG2 cells, we sought to verify its hepatoprotective effects and elucidate its mechanism in a TCDD-induced liver injury model in mice. MATERIAL AND METHODS: The mouse liver injury model was established by intraperitoneal TCDD injection, followed by treatment with various doses of ginsenoside Rg1 (50, 100, and 200 mg/kg). Clinical indicators of liver injury, such as an increase in serum aspartate aminotransferase and alanine aminotransferase levels, as well as histopathological changes were evaluated. RESULTS: The common clinical indicators of liver injury were detected following TCDD injection, including an increase in serum alanine aminotransferase and aspartate aminotransferase levels, increased relative liver weight, and histopathological changes. Following treatment with ginsenoside Rg1, the levels of aspartate aminotransferase and alanine aminotransferase decreased significantly, and the liver histology was improved. In addition, ginsenoside Rg1 competitively inhibited TCDD-induced Cyp1a1 mRNA transcription through the modulation of aryl hydrocarbon receptor (AhR) nuclear translocation. CONCLUSION: Ginsenoside Rg1 is a potent partial AhR agonist that has potential as an effective medication for protecting against TCDD-associated liver injury.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Panax , Dibenzodioxinas Policloradas , Alanina Transaminase , Animais , Aspartato Aminotransferases , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP1A1/genética , Ginsenosídeos , Fígado , Camundongos , Dibenzodioxinas Policloradas/toxicidade , Receptores de Hidrocarboneto Arílico/genéticaRESUMO
The present study aimed to investigate the protective role of capsaicin in a rat model of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD)-induced toxicity. Exposure to TCDD which is an environmental toxicant causes severe toxic effects in the animal and human tissues. Therefore, the potential protective effect of capsaicin in TCDD-induced organ damage was investigated in rats by measuring thiobarbituric acid reactive substances (TBARS) level, superoxide dismutase (SOD) activity, and glutathione (GSH) level in the heart, liver, and kidney tissues for oxidant/antioxidant balance. Thirty-two healthy adults (250-300 g weight and 3-4 months old) male Wistar albino rats were randomly distributed into four equal groups (n = 8): Control, CAP, TCDD, TCDD + CAP. A dose of 2 µg/kg TCDD or a dose of 25 mg/kg capsaicin were dissolved in corn oil and orally administered to the rats for 30 days. The results indicated that TCDD-induced oxidative stress by increasing the level of TBARS and by decreasing the levels of GSH, and SOD activity in the tissues of rats. However, capsaicin treatment was significantly decreased TBARS levels and was significantly increased GSH level and SOD activity (p < 0.05). In addition, capsaicin (25 mg/kg) significantly attenuated TCDD-induced histopathological alteration associated with oxidative stress in the heart, liver, and kidney tissues (p < 0.05). As capsaicin regulates oxidative imbalance and attenuates histopathological alterations in the rat tissues, it may be preventing agents in TCDD toxicity.
Assuntos
Dioxinas , Dibenzodioxinas Policloradas , Animais , Masculino , Ratos , Antioxidantes/farmacologia , Capsaicina/farmacologia , Óleo de Milho/farmacologia , Dioxinas/farmacologia , Glutationa/metabolismo , Oxidantes , Estresse Oxidativo , Dibenzodioxinas Policloradas/toxicidade , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
Activated charcoal (AC) is a potential candidate antidote against dioxins. However, it is difficult to take AC as a supplement on a daily basis, because its long-term ingestion causes side effects such as constipation and deficiency of fat-soluble essential nutrients and hypocholesterolemia. Alginate-coated AC, termed Health Carbon (HC), was developed to decrease the side effects of AC, but its pharmacological effects, including side effects, remains unclear. Here, we show that HC enhanced fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and decreased some side effects of unmodified AC, such as hypocholesterolemia, in male mice. Basal diet mixed with HC or unmodified AC at various concentrations was fed to mice for 16 days following a single intraperitoneal administration of [3H]TCDD. Both HC and unmodified AC at 3% or more significantly increased fecal excretion of [3H]TCDD in comparison with the control basal diet. Consistent with this, [3H]TCDD radioactivity in the liver-a major TCDD storage organ-was markedly decreased by HC at concentrations of 3% and 10%. In an examination of potential side effects, unmodified AC at 10% or more caused significant body weight reduction and at 20% caused significant hypocholesterolemia. In contrast, HC caused weight gain reduction only at a concentration of 20%, and there was no evidence of hypocholesterolemia at any dietary HC concentration. HC not only retains the ability of AC to enhance fecal excretion of TCDD but also reduces some of the side effects of AC.
Assuntos
Alginatos , Antídotos/efeitos adversos , Antídotos/farmacologia , Carvão Vegetal/efeitos adversos , Carvão Vegetal/farmacologia , Fezes , Dibenzodioxinas Policloradas/metabolismo , Administração Oral , Alginatos/administração & dosagem , Animais , Antídotos/administração & dosagem , Carvão Vegetal/administração & dosagem , Colesterol/sangue , Constipação Intestinal/induzido quimicamente , Masculino , Camundongos Endogâmicos , Redução de PesoRESUMO
INTRODUCTION: It is unknown if Agent Orange (AO)-exposed veterans have worse outcomes than unexposed Veterans after prostate cancer treatment. We evaluated oncologic outcomes based on AO exposure history, accounting for known prognostic covariates not previously studied. METHODS: US military Veterans diagnosed with prostate adenocarcinoma born between 1930 and 1956 were identified from our prospectively gathered institutional database. Evaluable patients had to have known AO exposure status, age, National Comprehensive Cancer Network risk group, Charlson comorbidity score, smoking status, and type of initial therapy. The risk of death, metastasis, and progression stratified by initial therapy was analyzed using Cox regression. RESULTS: Seventy AO-exposed and 561 non-exposed Veterans were identified (median follow-up, 10.0 years). AO-exposed veterans (AOeV) were slightly younger (64.0 vs 65.7 years; P = .013) at diagnosis and presented at more advanced stages (stage 4: 14.3% vs 2.5%) than non-AOeV. There was no difference for overall survival (hazard ratio [HR], 0.86; P = .576; metastasis-free survival (HR, 1.5; P = .212), or progression-free survival (HR, 0.67; P = .060) between AOeV vs non-AOeV in analyses stratified by treatment received accounting for other prognostic covariates. Cigarette smoking was associated with a 2- to 3-fold increased risk of death over those who quit or never smoked. CONCLUSION: Although AOeV do present at a younger age and higher clinical stages than non-AOeV, the oncologic outcomes after accounting for treatments received and other prognostic covariates are similar.
Assuntos
Dibenzodioxinas Policloradas , Neoplasias da Próstata , Veteranos , Ácido 2,4,5-Triclorofenoxiacético , Ácido 2,4-Diclorofenoxiacético , Agente Laranja , Humanos , Masculino , Neoplasias da Próstata/terapia , Estados Unidos/epidemiologiaRESUMO
Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho.
Assuntos
Dioxinas/intoxicação , Porfirias/induzido quimicamente , Porfirias/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Humanos , Espécies Reativas de Oxigênio/metabolismo , Óleo de Farelo de Arroz/efeitos adversosRESUMO
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent hepatic effects including lipid accumulation, inflammation, and fibrosis. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated. Female Sprague-Dawley (SD) rats were orally gavaged with sesame oil vehicle or 0.01-10 µg/kg TCDD every 4 days for 28 days. Hepatic RNA-Seq data was integrated with untargeted metabolomics of liver, serum, and urine, revealing dose-dependent changes in linoleic acid (LA) and arachidonic acid (AA) metabolism. TCDD also elicited dose-dependent differential gene expression associated with the cyclooxygenase, lipoxygenase, and cytochrome P450 epoxidation/hydroxylation pathways with corresponding changes in ω-6 (e.g. AA and LA) and ω-3 polyunsaturated fatty acids (PUFAs), as well as associated eicosanoid metabolites. Overall, TCDD increased the ratio of ω-6 to ω-3 PUFAs. Phospholipase A2 (Pla2g12a) was induced consistent with increased AA metabolism, while AA utilization by induced lipoxygenases Alox5 and Alox15 increased leukotrienes (LTs). More specifically, TCDD increased pro-inflammatory eicosanoids including leukotriene LTB4, and LTB3, known to recruit neutrophils to damaged tissue. Dose-response modeling suggests the cytochrome P450 hydroxylase/epoxygenase and lipoxygenase pathways are more sensitive to TCDD than the cyclooxygenase pathway. Hepatic AhR ChIP-Seq analysis found little enrichment within the regulatory regions of differentially expressed genes (DEGs) involved in eicosanoid biosynthesis, suggesting TCDD-elicited dysregulation of eicosanoid metabolism is a downstream effect of AhR activation. Overall, these results suggest alterations in eicosanoid metabolism may play a key role in TCDD-elicited hepatotoxicity associated with the progression of steatosis to steatohepatitis.
Assuntos
Eicosanoides/metabolismo , Ácidos Graxos Insaturados/metabolismo , Fígado/efeitos dos fármacos , Dibenzodioxinas Policloradas/farmacologia , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Fígado Gorduroso/metabolismo , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
This study investigates the occurrence of polybrominated biphenyls (PBBs), a legacy flame retardant, in fishery products such as medicinal grade cod liver oils and canned liver products, sourced from the North Atlantic during 1972-2017. It also assesses the dietary and supplementary (the oils were commonly administered as dietary supplements to children and youth) intake of PBBs from these products. Summed ortho-PBB concentrations ranged from 770 to 1400 pg g-1 fat in the oils and from 99 to 240 pg g-1 whole weight in canned livers, with PBB-49, 52, 101 and 153 accounting for most of these levels. Among the more toxic non-ortho-PBBs, PBB-126 and PBB-169 were not detected, but PBB-77 concentrations ranged from 0.6 to 5.78 pg g-1 fat in the oils and 0.06-0.126 pg g-1 whole weight in canned livers. During 1972-1993, PBB contamination levels were similar for cod liver oils from the Baltic Sea and other North Atlantic regions, but over the timescale of the study, Baltic Sea products appear to show a decline in PBB concentrations. As PBB-77 was the only dioxin-like PBB detected in the samples, the corresponding supplementary (oils, 1972-2001) and dietary (cod liver from 2017) intakes were very low, at < 0.001 pg TEQ kg-1 bm d-1 (or < 0.01 pg TEQ kg-1 bm d-1 upper bound) for the sum of all the measured dioxin-like PBBs -four to six orders of magnitude lower than that arising from other dioxin-like contaminants that were shown to occur in these products, from earlier studies.
Assuntos
Óleo de Fígado de Bacalhau/química , Alimentos em Conserva/análise , Gadus morhua/metabolismo , Fígado/química , Bifenil Polibromatos/análise , Poluentes Químicos da Água/análise , Adolescente , Animais , Países Bálticos , Criança , Dioxinas/metabolismo , Retardadores de Chama/metabolismo , Humanos , Fígado/metabolismo , Bifenil Polibromatos/química , Poluentes Químicos da Água/químicaRESUMO
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that produces a wide variety of adverse effects in humans. Catalpol, a major bioactive compound enriched in the dried root of Rehmannia glutinosa, is a major iridoid glycoside that alleviates bone loss. However, the detailed mechanisms underlying the effects of catalpol remain unclear. The present study evaluated the effects of catalpol on TCDD-induced cytotoxicity in osteoblastic MC3T3-E1 cells. Catalpol inhibited TCDD-induced reduction in cell viability and increases in apoptosis and autophagic activity in osteoblastic MC3T3-E1 cells. Additionally, pretreatment with catalpol significantly decreased the nitric oxide and nitrite levels compared with a control in TCDD-treated cells and significantly inhibited TCDD-induced increases in the levels of cytochrome P450 1A1 and extracellular signal-regulated kinase. Pretreatment with catalpol also effectively restored the expression of superoxide dismutase and extracellular signal-regulated kinase 1 and significantly enhanced the expression of glutathione peroxidase 4 and osteoblast differentiation markers, including alkaline phosphatase and osterix. Taken together, these findings demonstrate that catalpol has preventive effects against TCDD-induced damage in MC3T3-E1 osteoblastic cells.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Osteoblastos/efeitos dos fármacos , Dibenzodioxinas Policloradas/toxicidade , Substâncias Protetoras/farmacologia , Animais , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glucosídeos Iridoides/isolamento & purificação , Medicina Tradicional Chinesa , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Osteoblastos/metabolismo , Osteoblastos/patologia , Raízes de Plantas/química , Substâncias Protetoras/isolamento & purificação , Rehmannia/químicaRESUMO
We have studied the feasibility of solid phase extraction of PCDDs/PCDFs and dioxin-like PCBs from oils and fats as the first step of a sample preparation procedure that would not involve the chemical decomposition of the matrix. A few experimental setups using dual-layer columns packed with various brands of active carbon were tested. The use of a dual-layer microcolumn with AX-21 and Carboxen 1000 carbons for dioxins extraction from animal fats, vegetable oils and powdered milk gave satisfactory recoveries which met the European Union Commission Regulation 2017/644 criteria for dioxin analysis. The developed method of solid phase extraction on a dual-layer carbon column requires lower amounts of solvents and sorbents, tolerates high amounts of fat and can be used in both manual and automated sample preparation procedures. The recoveries obtained for the most toxic congeners (2,3,7,8-TCDD, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF) are within 79-119%.
Assuntos
Dibenzofuranos Policlorados/análise , Dioxinas/análise , Gorduras/química , Contaminação de Alimentos/análise , Óleos de Plantas/química , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análise , Extração em Fase Sólida/métodos , Animais , AlimentosRESUMO
National dietary guidelines are directed at the general population. However, these guidelines may be perceived as unrealistic by a substantial part of the population, as they differ considerably from individual consumption patterns and preferences. Personalised dietary recommendations will probably improve adherence, and it has been shown that these recommendations can be derived by mathematical optimisation methods. However, to better account for risks and benefits of specific foods, the background exposure to nutrients and contaminants needs to be considered as well. This background exposure may come from other foods and supplements, and also from environmental sources like the air and the sun. The objective of this study was therefore to analyse the effect of including individual variation in background exposure when modelling personalised dietary recommendations for fish. We used a quadratic programming model to generate recommended fish intake accounting for personal preference by deviating as little as possible from observed individual intake. Model constraints ensure that the modelled intake meets recommendations for EPA, DHA and vitamin D without violating tolerable exposure to methyl mercury, dioxins and dioxin-like polychlorinated biphenyls. Several background exposures were analysed for 3016 Danish adults, whose food intakes and body weights were reported in a national dietary survey. We found that the lower nutrient constraints were critical for the largest part of the study population, and that a total of 55% should be advised to increase their fish intake. The modelled fish intake recommendations were particularly sensitive to the vitamin D background exposure.
Assuntos
Dieta , Peixes , Contaminação de Alimentos , Alimentos Marinhos/análise , Adolescente , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poluentes Químicos da Água , Adulto JovemRESUMO
Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)â»cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch that induces the expression of various antioxidative enzymes, such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHRâ»CYP1A1 signaling and activates the NRF2â»antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHRâ»CYP1A1 inhibition and NRF2 activation may be useful for managing dioxin-related health hazards.
RESUMO
2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is a toxic agent and has disruptive effects on reproductive tissues in females. TCDD disrupts the hormonal regulation of the body and decreases the production of melatonin. In this study, we investigated the protective effects of melatonin supplements against the toxic effects of TCDD on ovaries of female rats. TCDD caused a significant decrease in the average number of corpora lutea and follicles per tissue section (2.1 ± 0.7; 2.3 ± 0.8, respectively), whereas these numbers were maintained in the melatonin supplemented group (5.0 ± 0.8; 5.1 ± 0.8, respectively) and were similar to the control group (5.3 ± 1.0; 5.9 ± 0.9, respectively). Electron microscopic analysis showed that the disruption of ultrastructure components such as cell membrane and organelles due to TCDD exposure was inhibited by melatonin supplements. This study suggested that melatonin has a protective and a possible ameliorative effect over histopathological damage of rat ovaries exposed to TCDD.
Assuntos
Herbicidas/toxicidade , Melatonina/farmacologia , Ovário/efeitos dos fármacos , Dibenzodioxinas Policloradas/toxicidade , Animais , Corpo Lúteo/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Feminino , Folículo Ovariano/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Many aquatic pollutants can be present at low concentrations, but their mixtures can still affect health or behavior of exposed organisms. In this study, toxicological and chemical analyses were combined for spatial contamination profiling using an innovative passive sampling approach. A novel Dynamic Passive Sampler (DPS) was employed as a mobile sampler from a ship cruising along 2130km of the Danube river during the Joint Danube Survey 3 (JDS3). The sampling was performed in eight subsequent river stretches with two types of complementary passive samplers: silicone rubber sheets (SR) used for non-polar chemicals and SDB-RPS Empore™ disks (ED) for more hydrophilic compounds. Besides extensive chemical analyses, the bioactivity of samples was characterized by a battery of reporter gene bioassays. Cross-calibration of the employed passive samplers enabled robust estimation of water concentrations applicable for compounds with a wide range of physicochemical properties. DPS was suitable for sampling of water contaminants even at pgL-1 levels, with 209 of 267 analyzed compounds detected in the samples. Biological effects were detected in both ED and SR extracts across all river stretches by bioassays focused on xenobiotic metabolism mediated by the aryl hydrocarbon and pregnane X receptors, endocrine disruptive potential mediated by estrogen and androgen receptors and the oxidative stress response. The bioassay responses expressed as bioanalytical equivalent concentrations (BEQbio) were comparable with data obtained from large volume active sampling. The extracts of the ED samplers were more biologically active than extracts of SR samplers. Except of estrogenicity, where the analyzed chemicals explained on average 62% of the effects in ED samples, the detected chemicals explained <8% of BEQbio values. The study shows the utility of the combination of the innovative passive sampling approach with effect-based tools for efficient and fast monitoring even in water bodies with relatively low levels of contamination.
Assuntos
Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Bioensaio , Monitoramento Ambiental/instrumentação , Estrogênios , Rios/químicaRESUMO
We determined the concentrations of dioxins (polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls) in 46 dietary supplement products, containing the oil of fish, marine mammals, or egg yolk, on the Japanese market between 2007 and 2014. Dioxins were detected in 43 of the 46 products tested at concentrations from 0.00015 to 67 pg TEQ/g. The highest concentration of dioxins was found in a shark liver oil product which varied insignificantly in five batches collected over a two-year period. The dioxin intakes from these five batches reached 2.3-2.8 pg TEQ/kg bw/day, or 58%-70%, respectively, of the Japanese tolerable daily intake (TDI) of 4 pg TEQ/kg bw/day. However, the dioxin intakes from most of the other products tested were less than 5% of the TDI. Although rare, supplements based on animal oils may contain relatively high concentrations of dioxins, leading to a substantial increase in dioxin intakes.
Assuntos
Exposição Dietética/estatística & dados numéricos , Suplementos Nutricionais/análise , Dioxinas/análise , Contaminação de Alimentos/análise , Animais , Benzofuranos/análise , Exposição Dietética/análise , Gema de Ovo/química , Óleos de Peixe , Peixes , Contaminação de Alimentos/estatística & dados numéricos , Humanos , Nível de Efeito Adverso não Observado , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análiseRESUMO
Dioxins, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are responsible for producing serious toxic effects in the next generation, such as sexual immaturity. Our laboratory found that treating pregnant rats on gestational day 15 with TCDD (1 µg/kg orally) targets pituitary luteinizing hormone (LH) to attenuate testicular steroidogenesis in fetuses. Because sex steroids during a short window ("the critical period") in the perinatal stage stimulate brain differentiation closely linked to sexual maturation, it is likely that TCDD imprints sexual immaturity on the offspring due to the lowered expression of LH during the fetal period. To address this hypothesis, we first investigated the effect of supplementation of equine chorionic gonadotropin (eCG), an LH-mimicking hormone, in fetuses exposed to TCDD. The result showed that eCG ameliorated defects in sexual behavior in adulthood as well as in steroidogenesis during the fetal stage. We also found that maternal exposure to TCDD induced the pituitary expression of histone deacetylases (HDACs) in fetuses. In agreement with this, TCDD deacetylated the histones wrapped around the LHß gene, and valproic acid, an HDAC inhibitor, blocked the reduced level of LHß caused by TCDD. These observations strongly suggest that TCDD induces the expression of HDACs to attenuate fetal LH production. Finally, such a transient reduction in steroidogenesis of the pituitary-gonadal axis causes a decrease in the expression of hypothalamic gonadotropin-releasing hormone, resulting in defects in sexual behavior in adulthood. This review increases our understanding of the developmental toxicities caused by endocrine disruptors including dioxins.
Assuntos
Dioxinas/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Exposição Materna/efeitos adversos , Troca Materno-Fetal , Efeitos Tardios da Exposição Pré-Natal , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/genética , Animais , Dioxinas/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Idade Gestacional , Hormônios Esteroides Gonadais/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Histona Desacetilases/metabolismo , Humanos , Hipotálamo/metabolismo , Recém-Nascido , Hormônio Luteinizante/metabolismo , Masculino , Hipófise/metabolismo , Gravidez , Ratos , Testículo/metabolismoRESUMO
Activated carbon (AC) is an increasingly attractive remediation alternative for the sequestration of dioxins at contaminated sites globally. However, the potential for AC to reduce the bioavailability of dioxins in mammals and the residing gut microbiota has received less attention. This question was partially answered in a recent study examining 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hallmark toxic responses in mice administered with TCDD sequestered by AC or freely available in corn oil by oral gavage. Results from that study support the use of AC to significantly reduce the bioavailability of TCDD to the host. Herein, we examined the bioavailability of TCDD sequestered to AC on a key murine gut commensal and the influence of AC on the community structure of the gut microbiota. The analysis included qPCR to quantify the expression of segmented filamentous bacteria (SFB) in the mouse ileum, which has responded to TCDD-induced host toxicity in previous studies and community structure via sequencing the 16S ribosomal RNA (rRNA) gene. The expression of SFB 16S rRNA gene and functional genes significantly increased with TCDD administered with corn oil vehicle. Such a response was absent when TCDD was sequestered by AC. In addition, AC appeared to have a minimal influence on murine gut community structure and diversity, affecting only the relative abundance of Lactobacillaceae and two other groups. Results of this study further support the remedial use of AC for eliminating bioavailability of TCDD to host and subsequent influence on the gut microbiome.
Assuntos
Carvão Vegetal/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Dibenzodioxinas Policloradas/administração & dosagem , Animais , Disponibilidade Biológica , Carvão Vegetal/farmacocinética , Óleo de Milho/administração & dosagem , Óleo de Milho/farmacocinética , Feminino , Íleo/microbiologia , Lactobacillaceae/metabolismo , Camundongos , Dibenzodioxinas Policloradas/farmacocinética , Dibenzodioxinas Policloradas/toxicidade , RNA Ribossômico 16S/genética , TranscriptomaRESUMO
The effectiveness of activated carbon in reducing the bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined from the context of using in situ sorbent amendments to remediate soils/sediments contaminated with polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs). This technology has gained rapid acceptance based on observations that activated carbon amendments predictably lower PCDD/F concentrations in water and bioaccumulation by simple aquatic organisms and earthworms; it has been assumed that bioavailability to mammals is similarly reduced, although this has been disproven for other sorbent materials. In the present study TCDD was absorbed to a microporous activated carbon (TCDD-AC) using the incipient wetness method. An aqueous suspension of TCDD-AC and an equivalent dosage of TCDD in corn oil were administered by oral gavage to B6C3F1 mice. The relative bioavailability of TCDD-AC was determined by quantifying and comparing the hepatic induction of cyp1A1 (messenger ribonucleic acid) and suppression of the immunoglobulin M antibody-forming cell immune response by the 2 forms of TCDD. A concentration-dependent response was observed for both assays when TCDD in corn oil was administered to mice. However, when equivalent masses of TCDD were administered as TCDD-AC, no induction of cyp1A1 or suppression of the immunoglobulin M antibody-forming cell response was observed. The absence of these 2 sensitive aryl hydrocarbon receptor-mediated responses in mice provides the first direct evidence that activated carbon can sequester TCDD in a form that eliminates its bioavailability to mammals. These results support the premise that activated carbon can be used to reduce the bioeffective dose of TCDD delivered to mammals and that activated carbon amendments may provide a low-cost alternative to traditional remediation technologies. Environ Toxicol Chem 2017;36:2671-2678. © 2017 SETAC.