Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 616
Filtrar
1.
Arh Hig Rada Toksikol ; 72(3): 182-190, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34587672

RESUMO

Even though the endocrine-disrupting potential of perfluorooctanoic acid (PFOA) is well known, the mechanisms underlying its cellular and epigenetic toxicity at the critical stage of hypothalamic development are poorly understood. This is why we studied its effects on the embryonic mouse hypothalamic cell line N46 (mHypoE-N46) with a hope to shed more light on the mechanisms through which PFOA causes embryonic hypothalamic cell damage. To do that, we studied cell viability, global DNA methylation, and gene expression in cells exposed to PFOA. As the PFOA dose increased, cell viability decreased, while global DNA methylation increased. PFOA also significantly altered the expression of genes related to the apoptosis and cell cycle, neurotrophic genes, and the Tet, Dnmt, and Mecp2 genes. Our findings suggest that exposure to PFOA affects cell survival through the reprogramming of embryonic hypothalamic DNA methylation patterns and altering cell homeostasis genes. DNA methylation and changes in the Mecp2 gene expression induced by PFOA also imply wider ramifications, as they alter genes of other major mechanisms of the embryonic hypothalamus. Our study may therefore serve as a good starting point for further research into the mechanisms of PFOA effect of hypothalamic development.


Assuntos
Caprilatos , Fluorcarbonetos , Animais , Caprilatos/toxicidade , Epigênese Genética , Fluorcarbonetos/toxicidade , Expressão Gênica , Camundongos
2.
Arch Environ Contam Toxicol ; 81(3): 470-481, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34545443

RESUMO

This study presents a comprehensive application of the probabilistic risk assessment methodology for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which are two types of perfluoroalkyl acids frequently studied in recent years. The exposure characteristics of PFOA and PFOS in Chinese surface water on a nationwide scale were summarized. Individual predicted no-effect concentration (PNEC) and the sensitivities for taxonomic groups of primary producers, invertebrates, and vertebrates were derived by the species sensitivity distributions method. Both hazard quotients (HQs) and joint probability curves were calculated to assess the risks to aquatic organisms. Among seven Chinese river basins, the mean concentrations of PFOA and PFOS in the Yangtze River Basin were the highest (58 ng/L and 22 ng/L, respectively), while the lowest concentrations (< 1 ng/L) were in the Songhua River Basin. The acute PNEC value was 2.43 mg/L for PFOA and 0.96 mg/L for PFOS, and the chronic PNEC value was 0.0067 mg/L for PFOA and 0.0012 mg/L for PFOS, respectively. The sensitivities of different taxonomic groups revealed higher sensitivity of primary producers for PFOA and higher sensitivity of invertebrates for PFOS. The acute HQs of PFOA and PFOS were less than 1. The probabilities of exposure concentrations exceeding 5th percentile toxicity value of the chronic data for all aquatic organisms were 1.65% for PFOA and 1.23% for PFOS, respectively, suggesting a low probability of effects to aquatic organisms. Compared with the risk scenarios worldwide, the ecological risks for chronic effects decreased in the order of PFOS (worldwide) > PFOA (China) > PFOS (China) > PFOA (worldwide).


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/análise , Ácidos Alcanossulfônicos/toxicidade , Animais , Caprilatos/toxicidade , China , Fluorcarbonetos/análise , Fluorcarbonetos/toxicidade , Medição de Risco , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
3.
Toxicol Lett ; 351: 155-162, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34517056

RESUMO

Perfluorooctanoic acid (PFOA), a member of the Per- and polyfluoroalkyl substances, is a highly persistent "forever" chemicals with increasing concern for its potential health effects. However, the mechanisms of PFOA immunotoxic effects are poorly understood. We assessed the antibody response to a physiological antigen stimulation and associated cytokine response upon PFOA exposure. The significant decrease in the IgM antibody response to the T cell dependent antigen keyhole limpet hemocyanin (KLH) at a dose lower than the previously documented LOAEL was accompanied by a significant reduction of the Th2 serum cytokines IL-5 and IL-13, a non-significant dose-response reduction of IL-4, a significant reduction of the Th1 cytokine IL-12, and a non-significant dose-response increase in IL-2 and IFNγ. PFOA significantly decreased the pro-inflammatory cytokines IL-17α and IL-1α, decreased (non-significantly but dose-response) IL-6, and a significantly increased TNFα. Overall, the modulation of serum Th1/Th2 cytokines could explain the reduction in antibody response, pointing to a potential role for T helper cells in the immunotoxicity of PFOA. Further, the higher than anticipated weight loss and increased liver weight, compared to previous studies using similar doses, highlight the potential importance of the route and duration of exposure, contributing to the total accumulated dose, in assessing the toxicity of PFOA.


Assuntos
Caprilatos/toxicidade , Citocinas/metabolismo , Fluorcarbonetos/toxicidade , Imunoglobulina M/metabolismo , Animais , Corticosterona/metabolismo , Citocinas/genética , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hemocianinas/imunologia , Camundongos
4.
Artigo em Inglês | MEDLINE | ID: mdl-34444092

RESUMO

Perfluorinated compounds (PFCs) are non-biodegradable synthetic chemical compounds that are widely used in manufacturing many household products. Many studies have reported the association between PFCs exposure with the risk of developing cardiovascular diseases (CVDs). However, those reports are still debatable, due to their findings. Thus, this review paper aimed to analyse the association of PFCs compound with CVDs and their risk factors in humans by systematic review and meta-analysis. Google Scholar, PubMed and ScienceDirect were searched for PFCs studies on CVDs and their risk from 2009 until present. The association of PFCs exposure with the prevalence of CVDs and their risk factors were assessed by calculating the quality criteria, odds ratios (ORs), and 95% confidence intervals (CIs). CVDs risk factors were divided into serum lipid profile (main risk factor) and other known risk factors. The meta-analysis was then used to derive a combined OR test for heterogeneity in findings between studies. Twenty-nine articles were included. Our meta-analysis indicated that PFCs exposure could be associated with CVDs (Test for overall effect: z = 2.2, p = 0.02; Test for heterogeneity: I2 = 91.6%, CI = 0.92-1.58, p < 0.0001) and their risk factors (Test for overall effect: z = 4.03, p < 0.0001; Test for heterogeneity: I2 = 85.8%, CI = 1.00-1.14, p < 0.0001). In serum lipids, total cholesterol levels are frequently reported associated with the exposure of PFCs. Among PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) exposure increased the risk of CVDs than other types of PFCs. Although the risk of PFOA and PFOS were positively associated with CVDs and their risk factors, more observational studies shall be carried out to identify the long-term effects of these contaminants in premature CVDs development in patients.


Assuntos
Ácidos Alcanossulfônicos , Doenças Cardiovasculares , Fluorcarbonetos , Caprilatos/toxicidade , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Fluorcarbonetos/toxicidade , Humanos
5.
Environ Pollut ; 288: 117707, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34252714

RESUMO

INTRODUCTION: The objective of this study was to validate the hypothesis that increased serum concentrations of perfluoroalkyl substances (PFASs) cause kidney damage. A causal interpretative study was designed using the US 2003-2018 National Health and Nutrition Examination Survey (NHANES) datasets. METHODS: Three statistical models, including multivariable linear regression, generalized additive model, and regression discontinuity model (RDM), were applied to the US 2003-2018 NHANES datasets to evaluate the causal relationship between the four PFAS agents and estimated glomerular filtration rate (eGFR). Directed acyclic graphs were plotted for a more valid causal inference. RESULTS AND DISCUSSION: In the RDM, when the natural logarithm of each PFAS agent increases by 1 ng/mL after each cut-off value, eGFR decreased 4.63 mL/min/1.73 m2 for perfluorooctanoic acid, 3.42 mL/min/1.73 m2 for perfluorooctane sulfonic acid, 2.37 mL/min/1.73 m2 for perfluorohexane sulfonic acid, and 2.87 mL/min/1.73 m2 for perfluorononanoic acid. The possibility of reverse causation that increased serum PFAS concentration is the consequence of reduced eGFR, not the cause, was low, and an additional adjustment of potential confounders was not needed. CONCLUSION: This study contributes to the understanding of PFAS-induced kidney damage. Further longitudinal epidemiological and toxicological studies are recommended.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorcarbonetos , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Rim , Inquéritos Nutricionais , Ácidos Sulfônicos
6.
Wei Sheng Yan Jiu ; 50(4): 609-614, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34311832

RESUMO

OBJECTIVE: To study the protective effect and mechanism of rutin on perfluorooctanoic acid(PFOA)-induced liver damage in mice. METHODS: A total of 24 male ICR mice were randomly divided into 3 groups, 8 in each group: control group(ctrl group: ddH_2O), perfluorooctanoic acid group(PFOA group: PFOA 20 mg/(kg·d)), rutin intervention group(rutin+PFOA group: PFOA 20 mg/(kg·d)+rutin 20 mg/(kg·d)), normal diet, oral gavage, daily observation, weighting, and recording. After 14 days of treatment, the liver was quickly stripped and weighted after blood sampling and execution. Part of the liver tissue is fixed in 4% paraformaldehyde for HE staining and PAS staining; glutamic-pyruvic transaminase(GPT) activity in the sera samples and triglyceride(TG), total cholesterol(TC), malondialhyde(MDA) content in hepatic tissue homogenate, as well as the activity of some enzymes were assayed; Using western blot to detect adenylate activated protein kinase α(AMPKα) and phosphorylated adenylate-activated protein kinase α(p-AMPKα) expression levels. RESULTS: PFOA caused a significant decrease in the weight of mice, a significant increase in liver weight and liver relative body weight coefficient(P& lt; 0.05), hepatocyte cord dissociation, hepatocyte swelling, dissolution, and obvious damage, and PAS staining positive result were significantly reduced. The GPT activity of the PFOA group was 204.63±11.26 U/L, which was significantly higher than that of the control group(28.80±4.51 U/L)(P& lt; 0.05); The contents of TG, TC and MDA in the liver tissues of mice were 4.89±0.51 mmol/g prot, 8.06±0.84 mmol/g prot and 315.38±60.79 nmol/mg prot, respectively, which were significantly higher than those of the control group(P& lt; 0.05); The activity of T-SOD was 4175.56±334.96 U/mg prot, which was significantly lower than that of the control group(P& lt; 0.05); After rutin intervention, compared with PFOA exposure group, the weight of the mice did not change significantly(P& gt; 0.05), however, the liver weight and the relative weight coefficient of the liver were significantly reduced(P& lt; 0.05), and the hepatocytes swollen and cell lysis were attenuated, the structure of cell cord changed clear, the positive PAS staining cells were significantly increased, the GPT activity of the rutin intervention group was 168.75±18.32 U/L, which was significantly lower than that of the PFOA group(P& lt; 0.05); The contents of TC and MDA in the liver tissues of mice were 4.25±0.77 mmol/g prot and 211.27±44.44 nmol/mg prot, respectively, which were significantly lower than those in the PFOA group(P& lt; 0.05); The T-SOD activity was 7368.88±673.09 U/mg prot, which was significantly higher than that of the PFOA group(P& lt; 0.05). There was no significant difference in AMPKα protein expression in the liver tissues of the three groups. Compared with the PFOA group, the p-AMPKα protein expression in the PFOA+rutin group was significantly up-regulated. CONCLUSION: PFOA exposure can cause liver damage and lipid accumulation in mice. Rutin has a certain protective effect on this damage, which may be related to rutin& apos; s activation of AMPKα protein expression to effectively correct TG levels and enhance the activity of antioxidant enzymes.


Assuntos
Caprilatos , Rutina , Animais , Caprilatos/toxicidade , Fluorcarbonetos , Fígado , Masculino , Camundongos , Camundongos Endogâmicos ICR
7.
Toxicology ; 459: 152845, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246716

RESUMO

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research.


Assuntos
Colesterol/sangue , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/sangue , Fluorcarbonetos/toxicidade , Ácidos Alcanossulfônicos/efeitos adversos , Ácidos Alcanossulfônicos/toxicidade , Animais , Caprilatos/efeitos adversos , Caprilatos/toxicidade , Determinação de Ponto Final , Fluorcarbonetos/efeitos adversos , Humanos
8.
Toxicol Appl Pharmacol ; 426: 115644, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34252412

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor α (hPPARα)-expressing mice fed an American diet. Mice were exposed to PFOA (3.5 mg/L) in drinking water for 6 weeks resulting in a serum concentration of 48 ± 9 µg/ml. In male and female hPPARα mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of PPARα alone also increased total liver TG, and PFOA treatment had little effect on liver TG in PPARα null mice. In hPPARα mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Intriguingly, in female PPARα null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPARα-dependent manner, but not in adipose. The results of our study and others reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.


Assuntos
Caprilatos/toxicidade , Dieta Ocidental , Dislipidemias/induzido quimicamente , Fluorcarbonetos/toxicidade , Fígado/efeitos dos fármacos , PPAR alfa/genética , Animais , Peso Corporal/efeitos dos fármacos , Dislipidemias/genética , Dislipidemias/metabolismo , Dislipidemias/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Genótipo , Lipidômica , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Transgênicos , Tamanho do Órgão/efeitos dos fármacos , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Estados Unidos
9.
Ecotoxicol Environ Saf ; 222: 112515, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34293584

RESUMO

Perfluorooctanoic acid (PFOA) is an environmental pollutant that has multiple toxic effects. Although some medicines and functional food ingredients are currently being used to alleviate the biological toxicity effects caused by PFOA, these candidates all show potential side effects and cannot prevent the accumulation of PFOA in the body, making them unable to be used as a daily dietary supplement to relieve the toxic effects of PFOA. However, new research has shown that lactic acid bacteria (LAB) can alleviate toxicity caused by exposure to foreign substances. In this study, multiple strains of LAB with different adsorption capacities or antioxidant capacities were used to analyse their mitigation effects of on liver damage caused by PFOA exposure. The results showed that the adsorption capacity and antioxidant capacity of LAB could alleviate the liver toxicity of PFOA to a certain extent. Moreover, treatment with some strains of LAB was able to recover the gut microbiota dysbiosis caused by PFOA exposure, such as by increasing the relative abundances of Patescibacteria, Proteobacteria, Akkermansia and Alistipes or decreasing the abundances of Bacteroides and Blautia. In addition, a strain with neither outstanding antioxidant capacity nor adsorption capacity also reversed the decline in short-chain fatty acid levels caused by PFOA exposure. The ability of these strains to relieve gut microbiota dysbiosis partly explains the inconsistency between the capacity for antioxidant or PFOA adsorption and the ability of the strains to alleviate PFOA toxicity. The results indicate that the PFOA adsorption capacity and antioxidant capacity of LAB may be involved in the alleviation of PFOA liver toxicity. In addition, LAB could also alleviate liver damage caused by PFOA by adjusting the gut microbiota and short-chain fatty acid content. Therefore, some strains of LAB can be used as a potentially safe dietary supplement to relieve PFOA-induced liver damage.


Assuntos
Fluorcarbonetos , Microbioma Gastrointestinal , Lactobacillales , Antioxidantes , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Fígado
10.
Environ Int ; 156: 106745, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34246126

RESUMO

Due to its potential adverse effects on human health, perfluorooctanoic acid (PFOA), one of the once widely used legacy per- and polyfluoroalkyl substances (PFASs), has been recently replaced by its novel alternatives including hexafluoropropylene-oxide-dimer-acid (GenX) and ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA). These alternative PFASs are detected in water and exposed workers. PFASs can enter organs like thyroids, however, it is yet unknown whether the new alternatives are safer than PFOA. In the current study, we compared the thyroid disrupting effects of PFOA and its alternatives GenX and ADONA in vitro with both rat thyroid cell line FRTL5 and primary normal human thyroid (NHT) cells. Cells were exposed to ascendant doses of PFOA, GenX or ADONA for various incubation time and cell viability was assessed by WST-1 assay and LDH assay. The proliferation rate of survived cells was determined by crystal violet-based cell proliferation assay and MTT assay. The gene expression of thyroid hormone regulation-related genes in thyroid cells after exposure was quantified by RT-PCR and Western blot. Our data showed that both PFOA and GenX reduced thyroid cell viability in both dose and time dependent manner, with GenX being more toxic than PFOA at the same condition. Similarly, the proliferation rate of cells survived exposure to PFOA and GenX was considerably impaired, with GenX showing more profound adverse effect than PFOA. Unlike PFOA and GenX, ADONA showed no apparent adverse effects on the viability and proliferation of both thyroid cell types. Gene expression data revealed that all three PFASs altered gene expression in both thyroid cells and the altered gene expression seemed to be PFAS and cell type dependent. Taken together, our data reveal that the thyroid disrupting effects is increased in the order of GenX > PFOA > ADONA. Our findings will be beneficial for the guidance of the future usage of PFASs and development of better alternatives.


Assuntos
Compostos de Amônio , Fluorcarbonetos , Adrenocromo/análogos & derivados , Animais , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Óxidos , Compostos de Amônio Quaternário , Ratos , Glândula Tireoide
11.
Toxicol Lett ; 349: 61-68, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34126183

RESUMO

Per and polifluorinated substances (PFAS) are ubiquitous and persistent contaminants. Studies have indicated that fetuses and infants can be exposed to these chemicals in utero and through breastfeeding. Despite this, limited data about their effects on brain development are available. Here, we compared the effects of perfluoroctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) exposure in rat primary neurons and neural stem cells (NSC). Treatment with 1-250 µM of either of these compounds caused no effects on cell viability or proliferation in primary neurons, while PFOS exposure increased the NSC proliferation already at the lowest concentration tested (1-100 µM). Further analysis showed that both PFOS and PFOA caused morphological alterations of NSC-derived neurons. The neurons derived from NSC treated with either of the PFAS demonstrated a decrease in cell body area. Exposure to 1 and 10 µM PFOA also affected the neurite network and caused an increase in the number of processes and branches per cell. None of the PFAS caused morphological alterations in primary neurons. These data suggest that NSC, mimicking the immature brain, is clearly more susceptible to PFOS and PFOA exposure than the primary neurons. The PFAS-induced alterations in NSC may be related to neurobehavioral alterations observed in rodents developmentally exposed to these compounds, and show the importance to consider the effects of these compounds on human brain development and disease.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Proliferação de Células/efeitos dos fármacos , Fluorcarbonetos/toxicidade , Células-Tronco Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Células Cultivadas , Células-Tronco Neurais/patologia , Neurônios/patologia , Cultura Primária de Células , Ratos Wistar
12.
Chemosphere ; 279: 130624, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34134420

RESUMO

Polyfluoroalkyl substances (PFASs), including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), are persistent pollutants routinely found in human blood. PFASs have been associated with health issues such as decreased birth weight and impaired vaccination response in children. Substitutes to these PFASs, such as ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate (GenX) have been introduced, although hazard information is limited. Human induced pluripotent stem cell (hiPSC) based models are valuable for studying these compounds, as they mimic human embryonic development. We used our recently developed PluriBeat assay to investigate PFOS, PFOA and GenX for effects on early embryonic development in vitro. In our assay hiPSCs go through the early stages of embryonic development in 3D cultures of embryoid bodies (EBs) that mimic the human blastocyst until they finally form beating cardiomyocytes. Both PFOS and PFOA had a strong effect on cardiomyocyte differentiation at non-cytotoxic concentrations, with PFOS being more potent than PFOA. Moreover, both compounds decreased EB size at the highest test concentrations. GenX induced a weak concentration-dependent effect on differentiation of one hiPSC line, but not of another. Transcriptional analysis of mRNA from the cardiomyocytes showed that PFOS increased expression of the early cardiac marker ISL1, whereas PFOA decreased expression of the cardiomyocyte marker MYH7. This suggest that PFOS and PFOA perturb cardiomyocyte differentiation by disrupting molecular pathways similar to those taking place in the developing embryo. Based on these findings, we conclude that our PluriBeat assay has the potential to become a valuable, sensitive model system for elucidating embryotoxic effects of PFASs in future.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Células-Tronco Pluripotentes Induzidas , Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Diferenciação Celular , Criança , Feminino , Fluorcarbonetos/toxicidade , Humanos , Gravidez
13.
Ecotoxicol Environ Saf ; 219: 112346, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34022627

RESUMO

Modified composite biochar offers a cost-effective solution for the remediation of contaminated sediments; however, few studies have evaluated the effects of modified composite biochar amendment on the ecotoxicity of contaminated sediment based on benthic macroinvertebrates. A 21-day sediment toxicity test was conducted using the freshwater snail Bellamya aeruginosa to examine the intrinsic ecotoxicity of a novel KOH-modified composite biochar (KOH-CBC) and its efficacy for reducing the bioavailability, uptake, and ecotoxicity of perfluorooctanoic acid (PFOA). It was found that KOH-CBC is toxic to B. aeruginosa, which may be attributed to its high polycyclic aromatic hydrocarbons (PAHs) content and alkalinity. The addition of KOH-CBC to PFOA-contaminated sediments can markedly reduce the bioavailability and uptake of PFOA by more than 90% and 50%, respectively, and subsequently alleviate the toxicity of PFOA to B. aeruginosa by at least 30%. Increasing the KOH-CBC dosage is not beneficial for further mitigating the toxicity of PFOA-contaminated sediments. Our findings imply that KOH-CBC is a promising sorbent for the in-situ remediation of PFOA-contaminated sediments. Application of acidified KOH-CBC at a dosage of approximately 1-3% will be sufficient to control the ecotoxicity of PFOA; however, its long-term environmental effects should be further validated.


Assuntos
Caprilatos/toxicidade , Recuperação e Remediação Ambiental/métodos , Fluorcarbonetos/toxicidade , Disponibilidade Biológica , Carvão Vegetal , Sedimentos Geológicos , Hidróxidos/química , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Compostos de Potássio/química , Pseudomonas aeruginosa
14.
Environ Toxicol Pharmacol ; 86: 103667, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33933708

RESUMO

Ingestion of perfluorooctanoic acid (PFOA) elicits toxicities in the hepatorenal system. We investigated the effect of PFOA and N-acetylcysteine (NAC) on the hepatorenal function of rats treated thus: control, PFOA (5 mg/kg), NAC (50 mg/kg), PFOA + NAC (5 and 25 mg/kg), and PFOA + NAC (5 and 50 mg/kg). We observed that NAC significantly (p < 0.05) reduced PFOA-induced increase in hepatic and renal function biomarkers of toxicities relative to PFOA alone and alleviated (p < 0.05) decreases in antioxidant status. Increases in oxidative stress and lipid peroxidation in PFOA-treated rats were reverted to normal by NAC and abated increased pro-inflammatory mediators, and decreased anti-inflammatory cytokine both in the hepatorenal system PFOA treated rats. Histology of the kidney and liver indicated that NAC, abated the severity of PFOA-induced damage significantly. Our findings affirm further that oxido-inflammatory mediators involved in PFOA-mediated toxicity can be effectively blocked by NAC through its antioxidant activity.


Assuntos
Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Acetilcisteína/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Creatinina/sangue , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Ratos Wistar , Ureia/sangue , gama-Glutamiltransferase/sangue
15.
Artigo em Inglês | MEDLINE | ID: mdl-33916482

RESUMO

Poly- and perfluoroalkyl substances (PFAS) are manmade synthetic chemicals which have been in existence for over 70 years. Though they are currently being phased out, their persistence in the environment is widespread. There is increasing evidence linking PFAS exposure to health effects, an issue of concern since PFAS such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) bioaccumulate in humans, with a half-life of years. Many epidemiological studies suggest that, worldwide, semen quality has decreased over the past several decades. One of the most worrying effects of PFOS and PFOA is their associations with lower testosterone levels, similar to clinical observations in infertile men. This review thus focuses on PFOS/PFOA-associated effects on male reproductive health. The sources of PFAS in drinking water are listed. The current epidemiological studies linking increased exposure to PFAS with lowered testosterone and semen quality, and evidence from rodent studies supporting their function as endocrine disruptors on the reproductive system, exhibiting non-monotonic dose responses, are noted. Finally, their mechanisms of action and possible toxic effects on the Leydig, Sertoli, and germ cells are discussed. Future research efforts must consider utilizing better human model systems for exposure, using more accurate PFAS exposure susceptibility windows, and improvements in statistical modeling of data to account for the endocrine disruptor properties of PFAS.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorcarbonetos , Infertilidade Masculina , Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/epidemiologia , Masculino , Saúde Reprodutiva , Análise do Sêmen
16.
J Hazard Mater ; 416: 125185, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-33882389

RESUMO

BACKGROUND: Perfluoroalkyl substances (PFASs) have been related to neurodevelopmental toxicity in animals. However, human studies are inconclusive. OBJECTIVES: To evaluate the association between prenatal PFAS exposure and neuropsychological development during childhood. METHODS: 1240 mother-child pairs from the Spanish INMA Project were analyzed. Perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) were measured in first-trimester maternal plasma. Neuropsychological development was assessed at 14 months, 4-5 and 7 years covering four domains: general cognitive, general motor, attention, and working memory. Associations were studied by means of multivariable regression analyses. RESULTS: PFHxS, PFOA, PFOS, and PFNA medians were: 0.6, 2.4, 6.1, and 0.7 ng/mL. Higher PFAS prenatal exposure was associated with worse motor development at 14 months, especially in the case of PFHxS (ß[95%CI]: -1.49[-2.73, -0.24]) and to a lesser extent PFOS (-1.25[-2.62, 0.12]). There was also a marginal positive association between general cognitive development at 4-5 years and PFOS (1.17[-0.10, 2.43]) and PFNA (0.99[-0.13, 2.12]). No clear associations for other neuropsychological outcomes or any sex differences were found. DISCUSSION: This study shows no clear-cut evidence of an association between prenatal PFAS exposure and adverse neuropsychological development in children up to the age of 7 years.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorcarbonetos , Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Criança , Feminino , Fluorcarbonetos/toxicidade , Humanos , Masculino , Gravidez , Primeiro Trimestre da Gravidez , Ácidos Sulfônicos
17.
Environ Toxicol Pharmacol ; 86: 103652, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33812015

RESUMO

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of perfluoroalkyl substances (PFAS). This study aimed to determine the protective role of Nrf2 against the toxicity of these agents. Nrf2-/- and wild-type astrocytes were exposed to PFOS (75-600 µM) and PFOA (400-1000 µM) for 24 h. Lactate dehydrogenase (LDH) release was significantly higher in nrf2-/- than in the wild-type astrocytes. Exposure to 600 µM PFOS and 800 µM PFOA showed significant increases in reactive oxygen species, lipid peroxidation, and apoptosis in nrf2-/- astrocytes as compared to wild-type astrocytes. The GSH/GSSG ratio was significantly decreased in nrf2-/- astrocytes when compared to wild-type astrocytes. Additionally, PFOS and PFOS caused dramatic ultrastructural alterations to the mitochondria. BHT pretreatment in wild-type cells decreased ROS production with exposure to both agents. Results of the present study conclude that PFOS and PFOA are cytotoxic to astrocytes and that nrf2 -/- cells are more sensitive to toxicity by these agents.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Astrócitos/efeitos dos fármacos , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Fator 2 Relacionado a NF-E2/genética , Animais , Apoptose/efeitos dos fármacos , Astrócitos/metabolismo , Células Cultivadas , L-Lactato Desidrogenase/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
18.
Ecotoxicol Environ Saf ; 215: 112128, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773150

RESUMO

Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macrophage RAW264.7. We assessed the effects of PFOA exposure on macrophage cell viability, cell apoptosis and cellular ROS level, and detected prominent cytokines release by RAW264.7. The results indicated that the cell viability of macrophage RAW264.7 was decreased by PFOA in dose- and time-dependent manners. Specifically, the exposure of 200 µM PFOA significantly increased apoptosis and ROS generation in macrophage, and thus caused cell damage. The ELISA results displayed that 100 µM PFOA exposure induced macrophage activation and enhanced cytokines secretion, including TNF-α, IL-1, IL-6, and IL-12. We also conducted nontargeted metabolomics based on LC-MS/MS and unveiled the perturbed metabolic pathways in macrophages induced by sublethal doses of PFOA (10 µM and 100 µM). Remarkably, global metabolomics results displayed that 10 µM PFOA exposure affected glutamine related pathways and the exposure at 100 µM conspicuously changed glutathione and fatty acid oxidation metabolism. These findings showed that 10 µM PFOA exposure could impel metabolic reprogramming of macrophage to trigger inflammatory response, although such dose displayed no obvious effect on cell viability, cellular ROS or apoptosis events of macrophage RAW264.7.


Assuntos
Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Cromatografia Líquida , Citocinas , Metabolismo dos Lipídeos , Macrófagos/fisiologia , Metabolômica , Transdução de Sinais , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa
19.
Fish Shellfish Immunol ; 113: 9-19, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33727078

RESUMO

Perfluorooctanoic acid (PFOA) is widely used in industrial production due to its stable chemical structure and hydrophobic and oleophobic characteristics. PFOA has been frequently detected in environmental media and organisms, leading to increased health risks. There is a lack of information about the immunotoxicity of aquatic organisms induced by PFOA, and the molecular mechanisms remain unclear. In this study, LC-MS analysis proved that PFOA can accumulate in the kidney of zebrafish. In the 0.05 mg/L PFOA treatment group, the accumulation of PFOA in the kidney after 21 days of exposure significantly increased by 79.89%, compared to 14 days of exposure. And a hydropic endoplasmic reticulum, swelling of mitochondria and vacuolization were observed in kidney immune cells of zebrafish. The Toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (myd88)/NF-κB (P65) pathway was activated when PFOA exerted its effects, which led to regulation of antibody expression; RT-PCR results showed that the mRNA expression level of interleukin-4 (IL-4) decreased in a dose-dependent manner, decreasing to 29.6% of the control level in the 1 mg/L PFOA group after 21 d of exposure. According to triangle plot analysis, immunoglobulin exhibited a notable stress response to PFOA at an early phase; a high concentration of PFOA may disrupt the immune system of zebrafish. Third-order polynomial fitting analysis showed that the high-mRNA-expression regions of IL-4 and antibodies were partially consistent. The results indicated that PFOA could affect antibodies by increasing the concentrations of proinflammatory cytokines. Changes in antibody levels further influenced the expression of other cytokines, which eventually caused disorders in the zebrafish immune system. This study expands the understanding of PFOA-induced immunosuppression and suggests that toxicity mechanisms should be considered for further health risk assessment of emerging pollutants.


Assuntos
Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Imunotoxinas/toxicidade , NF-kappa B/imunologia , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/imunologia , Animais , Rim/efeitos dos fármacos , Rim/imunologia , Transdução de Sinais/imunologia
20.
Environ Int ; 153: 106524, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33773143

RESUMO

BACKGROUND AND OBJECTIVE: The growing impact of the COVID-19 pandemic has heightened the urgency of identifying individuals most at risk of infection. Per- and poly-fluoroalkyl substances (PFASs) are manufactured fluorinated chemicals widely used in many industrial and household products. The objective of this case-control study was to assess the association between PFASs exposure and COVID-19 susceptibility and to elucidate the metabolic dysregulation associated with PFASs exposure in COVID-19 patients. METHODS: Total 160 subjects (80 COVID-19 patients and 80 symptom-free controls) were recruited from Shanxi and Shandong provinces, two regions heavily polluted by PFASs in China. Twelve common PFASs were quantified in both urine and serum. Urine metabolome profiling was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: In unadjusted models, the risk of COVID-19 infection was positively associated with urinary levels of perfluorooctanesulfonic acid (PFOS) (Odds ratio: 2.29 [95% CI: 1.52-3.22]), perfluorooctanoic acid (PFOA) (2.91, [1.95-4.83], and total PFASs (∑ (12) PFASs) (3.31, [2.05-4.65]). After controlling for age, sex, body mass index (BMI), comorbidities, and urine albumin-to-creatinine ratio (UACR), the associations remained statistically significant (Adjusted odds ratio of 1.94 [95% CI: 1.39-2.96] for PFOS, 2.73 [1.71-4.55] for PFOA, and 2.82 [1.97-3.51] for ∑ (12) PFASs). Urine metabolome-PFASs association analysis revealed that 59% of PFASs-associated urinary endogenous metabolites in COVID-19 patients were identified to be produced or largely regulated by mitochondrial function. In addition, the increase of PFASs exposure was associated with the accumulation of key metabolites in kynurenine metabolism, which are involved in immune responses (Combined ß coefficient of 0.60 [95% CI: 0.25-0.95, P = 0.001]). Moreover, alternations in PFASs-associated metabolites in mitochondrial and kynurenine metabolism were also correlated with clinical lab biomarkers for mitochondrial function (serum growth/differentiation factor-15) and immune activity (lymphocyte percentage), respectively. CONCLUSION: Elevated exposure to PFASs was independently associated with an increased risk of COVID-19 infection. PFASs-associated metabolites were implicated in mitochondrial function and immune activity. Larger studies are needed to confirm our findings and further understand the underlying mechanisms of PFASs exposure in the pathogenesis of SARS-CoV2 infection.


Assuntos
Ácidos Alcanossulfônicos , COVID-19 , Poluentes Ambientais , Fluorcarbonetos , Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Estudos de Casos e Controles , China/epidemiologia , Cromatografia Líquida , Poluentes Ambientais/toxicidade , Fluorcarbonetos/análise , Fluorcarbonetos/toxicidade , Humanos , Pandemias , RNA Viral , SARS-CoV-2 , Espectrometria de Massas em Tandem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...