RESUMO
Chlorinated polyfluorinated ether sulfonate (F-53B), a substitute of perfluorooctane sulfonic acid (PFOS), has attracted significant attention for its link to hepatotoxicity and enterotoxicity. Nevertheless, the underlying mechanisms of F-53B-induced enterohepatic toxicity remain incompletely understood. This study aimed to explore the role of F-53B exposure on enterohepatic injury based on the gut microbiota, pathological and molecular analysis in mice. Here, we exposed C57BL/6 mice to F-53B (0, 4, 40, and 400 µg/L) for 28 days. Our findings revealed a significant accumulation of F-53B in the liver, followed by small intestines, and feces. In addition, F-53B induced pathological collagen fiber deposition and lipoid degeneration, up-regulated the expression of fatty acid ß-oxidation-related genes (PPARα and PPARγ, etc), while simultaneously down-regulating pro-inflammatory genes (Nlrp3, IL-1ß, and Mcp1) in the liver. Meanwhile, F-53B induced ileal mucosal barrier damage, and an up-regulation of pro-inflammatory genes and mucosal barrier-related genes (Muc1, Muc2, Claudin1, Occludin, Mct1, and ZO-1) in the ileum. Importantly, F-53B distinctly altered gut microbiota compositions by increasing the abundance of Akkermansia and decreasing the abundance of Prevotellaceae_NK3B31_group in the feces. F-53B-altered microbiota compositions were significantly associated with genes related to fatty acid ß-oxidation, inflammation, and mucosal barrier. In summary, our results demonstrate that F-53B is capable of inducing hepatic injury, ileitis, and gut microbiota dysbiosis in mice, and the gut microbiota dysbiosis may play an important role in the F-53B-induced enterohepatic toxicity.
Assuntos
Microbioma Gastrointestinal , Ileíte , Camundongos , Animais , Disbiose , Peixe-Zebra/metabolismo , Camundongos Endogâmicos C57BL , Fígado , Ácidos Graxos/metabolismoRESUMO
Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6â¯J female mice were randomly allocated to three groups: the control group, F-53B 0.8⯵g/kg/day group, and F-53B 8⯵g/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8⯵g/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8⯵g/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.
Assuntos
Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Placenta , Animais , Feminino , Gravidez , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Placenta/efeitos dos fármacos , Placenta/patologia , Camundongos , Inflamassomos/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/patologia , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Fluorocarbonos/toxicidade , Transdução de Sinais/efeitos dos fármacosRESUMO
Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (µIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Alcanossulfonatos , Animais , Teorema de Bayes , China/epidemiologia , Estudos Transversais , Éter , Éteres , Fluorocarbonos/análise , Glândula Tireoide , Hormônios Tireóideos , TireotropinaRESUMO
The adverse effects of triphenyltin (TPT) on aquatic systems have attracted much attention because TPT is widely used and prevalent in aquatic environments. Here, zebrafish embryos/larvae were exposed to TPT (0, 0.039, 0.39, and 3.9 nM; 0, 15, 150 and 1500 ng/L) for 7 or 14 days to determine its toxic effects on the hypothalamic-pituitary-thyroid (HPT) axis. The results showed that whole-body total T4 and T3 levels were significantly decreased, which was accompanied by the significant upregulation of the expression of the dio1, dio2 and ugt1ab genes after exposure to TPT for 7 and 14 days. Genes related to thyroid hormone synthesis (crh, tshß, nis, tpo and tg) were upregulated at both 7 and 14 days after TPT exposure. This might have been due to the positive feedback regulation of the HPT axis, which is caused by a decrease in thyroid hormone in the whole body in zebrafish. In addition, the survival rates and body lengths were reduced after treatment with TPT for 7 and 14 days. This indicated that TPT caused adverse effect on the development of zebrafish embryos/larvae. In summary, the results suggested that TPT caused thyroid disruption and developmental toxicity in zebrafish larvae.
Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Larva/efeitos dos fármacos , Compostos Orgânicos de Estanho/toxicidade , Doenças da Glândula Tireoide/induzido quimicamente , Peixe-Zebra , Animais , Disruptores Endócrinos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Metamorfose Biológica/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Análise de Sobrevida , Glândula Tireoide/efeitos dos fármacos , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
Although polybrominated diphenyl ethers (PBDEs) are known to disturb thyroid hormone signaling, the mechanisms underlying the effects of 2,2',4,4'5 - pentain polybrominated diphenyl ethers (BDE-99) in fish remain unclear. In order to reveal these mechanisms, adult zebrafish (Danio rerio) were exposed to different concentrations of BDE-99 (0, 0.5, 5, or 50⯵g/L) for 28â¯days and spawned by mating naturally in clean water (without BDE-99). Females exposed to BDE-99 showed significantly lowered thyroxine (T4) levels. Expression of transthyretin (ttr) and uridine diphosphate glucuronosyl transferase (ugt1ab) were down-regulated and up-regulated, respectively. Triiodothyronine (T3) levels in the 0.5⯵g/L BDE-99 exposure group was significantly increased. Males showed significantly increased T3 levels, and lowered T4 levels, which were associated with up-regulated and down-regulated expression of deiodinase 2 (deio2) and ugt1ab, respectively. Exposure of adult zebrafish to BDE-99 lead to significantly increased T4 in the 0.5⯵g/L BDE-99 exposure group, but in the 50⯵g/L BDE-99 exposure group there was significantly reduced T4 in F1 larvae and altered mRNA transcription in the hypothalamic-pituitary-thyroid-liver (HPTL) axis. The offspring also showed reduced survival rates, and body length and elevated malformation rates. This study is the first in zebrafish to show that parental zebrafish exposure to BDE-99 can lead to developmental toxicity and thyroid disruption in the offspring.
Assuntos
Embrião não Mamífero/efeitos dos fármacos , Éteres Difenil Halogenados/toxicidade , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Relação Dose-Resposta a Droga , Embrião não Mamífero/anormalidades , Embrião não Mamífero/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pré-Albumina/genética , Pré-Albumina/metabolismo , Medição de Risco , Glândula Tireoide/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Epidemiological evidence showed that serum high perfluorooctane sulfonate (PFOS) levels are associated with multiple eye related diseases, but the potential underlying molecular mechanisms remain poorly understood. Zebrafish and photoreceptor cell (661w) models were used to investigate the molecular mechanism of PFOS induced eye development defects. Our results showed a novel molecular mechanism of PFOS-induced inflammation response-mediated photoreceptor cell death associated with eye development defects. Inhibition of Caspase-8 activation significantly decreased photoreceptor cell death in PFOS exposure. Mechanistically, Toll-like receptor 4 (TLR4) mediates activation of Caspase-8 promote activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome to elicit maturation of interleukin-1 beta (IL-1ß) via Caspase-1 activation, facilitating photoreceptor cell inflammation damage in PFOS exposure. In addition, we also made a novel finding that Caspase-3 activation was increased via Caspase-8 activation and directly intensified cell death. Our results show the important role of Caspase-8 activation in PFOS induced eye development defects and highlight Caspase-8 mediated activation of the NLRP3 inflammation triggers activation of Caspase-1 and promote the maturation of IL-1ß in retinal inflammatory injury.
Assuntos
Ácidos Alcanossulfônicos , Caspase 8 , Fluorocarbonos , Inflamassomos , Larva , Proteína 3 que Contém Domínio de Pirina da Família NLR , Peixe-Zebra , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Caspase 8/metabolismo , Caspase 8/genética , Ácidos Alcanossulfônicos/toxicidade , Fluorocarbonos/toxicidade , Larva/efeitos dos fármacos , Interleucina-1beta/metabolismo , Olho/efeitos dos fármacos , Poluentes Químicos da Água/toxicidadeRESUMO
Polycyclic aromatic hydrocarbons (PAHs) are well-known contaminants with widespread distribution in environment and food. Phenanthrene is one of the most abundant PAHs in food and aquatic environment and generates reproductive and developmental toxicity in zebrafish. Nonetheless, whether phenanthrene caused sex-specific thyroid disruption in adult zebrafish is unclear. To determine this, adult zebrafish (male and female) were treated with phenanthrene (0, 0.85, 8.5, and 85 µg/L) for 60 days. After the treatment period, we assessed the concentrations of thyroid hormones (THs) and expression levels of genes in the hypothalamic-pituitary-thyroid (HPT) axis. The results showed that phenanthrene exposure can lead to thyroid disruption in both male and female zebrafish. Exposure to phenanthrene dramatically reduced the levels of L-thyroxine (T4) and L-triiodothyronine (T3) in both male and female zebrafish, with a similar trend in both. However, the genes expression profiles of hypothalamic-pituitary-thyroid (HPT) axis were sex-specific. In all, the present study demonstrated that phenanthrene exposure could result in sex-specific thyroid disruption in adult zebrafish.
Assuntos
Fenantrenos , Poluentes Químicos da Água , Animais , Feminino , Masculino , Peixe-Zebra/metabolismo , Glândula Tireoide/metabolismo , Tri-Iodotironina/metabolismo , Tiroxina/metabolismo , Hormônios Tireóideos/metabolismo , Fenantrenos/toxicidade , Fenantrenos/metabolismo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
Maternal exposure to environment toxicants is an important risk factor for neurobehavioral health in their offspring. In our study, we investigated the impact of maternal exposure to chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs, commercial name: F-53B) on behavioral changes and the potential mechanism in the offspring larvae of zebrafish. Adult zebrafish exposed to Cl-PFESAs (0, 0.2, 2, 20 and 200 µg/L) for 21 days were subsequently mated their embryos were cultured for 5 days. Higher concentrations of Cl-PFESAs in zebrafish embryos were observed, along with, reduced swimming speed and distance travelled in the offspring larvae. Molecular docking analysis revealed that Cl-PFESAs can form hydrogen bonds with brain-derived neurotropic factor (BDNF), protein kinase C, alpha, (PKCα), Ca2+-ATPase and Na, K - ATPase. Molecular and biochemical studies evidenced Cl-PFESAs induce dopaminergic dysfunction, eye developmental defects and disrupted Ca2+ homeostasis. Together, our results showed that maternal exposure to Cl-PFESAs lead to behavioral alteration in offspring mediated by disruption in Ca2+ homeostasis, dopaminergic dysfunction and eye developmental defects.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Animais , Feminino , Peixe-Zebra/metabolismo , Ácidos Alcanossulfônicos/metabolismo , Cálcio/metabolismo , Larva , Simulação de Acoplamento Molecular , Fluorocarbonos/metabolismo , Poluentes Químicos da Água/metabolismo , Adenosina Trifosfatases/metabolismoRESUMO
BACKGROUND: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation. METHODS: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 µg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice. RESULTS: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was -2.47 (95 % CI: -3.89, -1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P < 0.001) in the target quadrant, as observed from morris water maze (MWM) test. The protein expression of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) levels were decreased, as compared to control (0.367-fold, P < 0.001; 0.366-fold, P < 0.001; respectively). We also observed the upregulation of dopamine transporter (DAT) (2.940-fold, P < 0.001) consistent with the trend of dopamine content (1.313-fold, P < 0.001) in the hippocampus. CONCLUSION: Early life exposure to F-53B is associated with adverse neurobehavioral changes in developing children and weaning mice which may be modulated by dopamine-dependent synaptic plasticity.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Humanos , Gravidez , Criança , Feminino , Animais , Camundongos , Alcanossulfonatos , Ácidos Alcanossulfônicos/toxicidade , Dopamina/análise , Dopamina/metabolismo , Desmame , Peixe-Zebra/metabolismo , Poluentes Químicos da Água/análise , Fluorocarbonos/toxicidade , Placenta/químicaRESUMO
Environmental pollutants exposure might disrupt cardiac function, but evidence about the associations of per- and polyfluoroalkyl substances (PFASs) exposure and cardiac conduction system remains sparse. To explore the associations between serum PFASs exposure and electrocardiogram (ECG) parameters changes in adults, we recruited 1229 participants (mean age: 55.1 years) from communities of Guangzhou, China. 13 serum PFASs with detection rate > 85% were analyzed finally. We selected 6 ECG parameters [heart rate (HR), PR interval, QRS duration, Bazett heart rate-corrected QT interval (QTc), QRS electric axis and RV5 + SV1 voltage] as outcomes. Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) model were conducted to explore the associations of individual and joint PFASs exposure and ECG parameters changes, respectively. We detected significant associations of PFASs exposure with decreased HR, QRS duration, but with increased PR interval. For example, at the 95th percentile of 6:2 Cl-PFESA, HR and QRS duration were - 6.98 [95% confidence interval (CI): - 9.07, - 4.90] and - 6.54(95% CI: -9.05, -4.03) lower, but PR interval was 7.35 (95% CI: 3.52, 11.17) longer than those at the 25th percentile. Similarly, significant joint associations were observed in HR, PR interval and QRS duration when analyzed by BKMR model.
Assuntos
Poluentes Ambientais , Fluorocarbonos , Humanos , Adulto , Pessoa de Meia-Idade , Teorema de Bayes , Exposição Ambiental , Eletrocardiografia , Fluorocarbonos/toxicidadeRESUMO
Phenanthrene induces reproductive and developmental toxicity in fish, but whether it can disrupt the thyroid hormone balance and inhibit growth had not been determined to date. In this study, zebrafish embryos were exposed to phenanthrene (0, 0.1, 1, 10 and 100 µg/L) for 7 days. The results of this experiment demonstrated that phenanthrene induced thyroid disruption and growth inhibition in zebrafish larvae. Phenanthrene significantly decreased the concentration of l-thyroxine (T4) but increased that of 3,5,3'-l-triiodothyronine (T3). The expression of genes related to the hypothalamic-pituitary-thyroid (HPT) axis was altered in zebrafish larvae exposed to phenanthrene. Moreover, phenanthrene exposure significantly increased the malformation rate and significantly reduced the survival rate and the body length of zebrafish larvae. Furthermore, phenanthrene significantly decreased the concentrations of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Changes observed in gene expression patterns further support the hypothesis that these effects may be related to alterations along the GH/IGF-1 axis. In conclusion, our study indicated that exposure to phenanthrene at concentrations as low as 0.1 µg/L resulted in thyroid disruption and growth inhibition in zebrafish larvae. Therefore, the estimation of phenanthrene levels in the aquatic environment needs to be revisited.
Assuntos
Fenantrenos , Poluentes Químicos da Água , Animais , Larva , Fenantrenos/toxicidade , Glândula Tireoide , Poluentes Químicos da Água/toxicidade , Peixe-ZebraRESUMO
Copper (Cu2+) and zinc (Zn2+) are two kinds of heavy metals essential to living organisms. Cu2+ and Zn2+ at excessive concentrations can cause adverse effects on animals, but little is known about the thyroid-disrupting effects of these metals in fish, especially in the early developmental transition stage from embryos to larvae. Wild-type zebrafish embryos were used to expose to Cu2+ (0, 1.5, 15, and 150 µg/L) and Zn2+ (0, 20, 200, and 2000 µg/L) for 120 h. Thyroid hormone contents and transcriptional changes of the genes connected with the hypothalamic-pituitary-thyroid (HPT) axis were measured. Results showed that zebrafish embryos/larvae malformation rates were significantly increased in the Cu2+ and Zn2+ groups. Remarkably elevated thyroxine (T4) concentrations and reduced triiodothyronine (T3) concentrations were observed in Cu2+ and Zn2+ exposure fish. And the expression patterns of genes connected with the HPT axis were changed after Cu2+ and Zn2+ treatment. Based on principal component analysis (PCA) results, Zn2+ caused significant effects on the thyroid endocrine system at 200 µg/L, while Cu2+ resulted in thyroid disruption as low as 1.5 µg/L. In short, our study demonstrated that exposure to Cu2+ and Zn2+ induced developmental toxicity and thyroid disruption to zebrafish embryos/larvae.
RESUMO
The perfluorooctane sulfonate alternative, F-53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F-53B at four different concentrations (0, 0.15, 1.5, and 15 µg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F-53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53, casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa, crybb, crygn, and mipa) and retinal development (pax6, rx1, gant1, rho, opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F-53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Acetilcolina , Laranja de Acridina/análise , Alcanossulfonatos/análise , Animais , Dopamina , Larva , Retinoides , Tretinoína , Proteína Supressora de Tumor p53 , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Ácidos Alcanossulfônicos/análise , Ácidos Alcanossulfônicos/toxicidade , Teorema de Bayes , China/epidemiologia , Estudos Transversais , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Fluorocarbonos/análise , Fluorocarbonos/toxicidade , Humanos , Fígado/químicaRESUMO
Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , China/epidemiologia , Fluorocarbonos/análise , Lipídeos , Projetos de PesquisaRESUMO
It has been reported that exposure to perfluorooctane sulfonates (PFOS) causes behavioral abnormalities in zebrafish larvae, but the possible mechanisms underlying these changes remain unexplored. In this study, zebrafish embryos (2 h postfertilization, 2-hpf) were exposed to PFOS at different concentrations (0, 0.032, 0.32 and 3.2 mg/L) for 120 h. Developmental endpoints and the locomotion behavior of larvae were evaluated. Reactive oxygen species (ROS) levels, dopamine contents, several genes and proteins related to neurodevelopment and dopamine signaling were examined. Our results indicate that increased ROS levels in the zebrafish larvae heads may be causally associated with neurodevelopment damage. Meanwhile, brain-derived neurotrophic factor (BDNF) and alpha1-Tubulin (α1-Tubulin) protein contents were significantly increased, which may be a compensatory mechanism for the impaired central nervous system. PFOS-induced locomotor hyperactivity was observed in the first light phase and dark phase at the 0.32 and 3.2 mg/L of PFOS. Upregulation of dopamine-related genes tyrosine hydroxylase (th) and dopamine transporter (dat) associated with increased dopamine contents in the 3.2 mg/L of PFOS. In addition, protein expression of TH and DAT were noted at the 0.32 and 3.2 mg/L of PFOS concentrations. Our results suggested that PFOS induces neurobehavioral changes in zebrafish larvae, possibly by perturbing a dopamine signaling pathway. In addition, PFOS induced development damage, such as increased malformation rate and shorter body length.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/metabolismo , Ácidos Alcanossulfônicos/toxicidade , Animais , Dopamina/metabolismo , Embrião não Mamífero/metabolismo , Fluorocarbonos/metabolismo , Fluorocarbonos/toxicidade , Larva/metabolismo , Neurotransmissores/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tubulina (Proteína)/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismoRESUMO
Although organotin compounds are known to disturb thyroid signaling and antioxidant defense system, the sex-differences underlying these effects of triphenyltin chloride (TPT) in fish remain unclear. To understand these differences, adult zebrafish (Danio rerio) were exposed to different concentrations of TPT (0, 10, 100, or 1000 ng/L) for 28 days. Female zebrafish exposed to TPT showed significantly increased thyroxine (T4) content and decrease triiodothyronine (T3) content, possibly due to downregulation of deiodinase (dio2) and uridine diphosphate glucuronosyl transferase (ugt1ab). However, decreased T4 and T3 contents in male zebrafish accompanied with upregulation of dio1, dio2 and ugt1ab. TPT exposure can lead to sex-specific thyroid disruption in adult zebrafish via alterations the Hypothalamus-pituitary-thyroid-liver axis. In addition, the gene expression levels of metabolizing enzymes, such as cyp1b, cyp1c, gpx1a, or sult1st1 were also to vary in a sex-dependent manner in adult zebrafish liver. Downregulation of cyp19a and cyp19b and decreased 17ß-estradiol (E2) contents were detected in both female and male zebrafish. Therefore, a sex-specific of thyroid disruption response after TPT exposure was observed in adult zebrafish, possibly due to inherent in female or males detoxifying enzyme capacities.
Assuntos
Disruptores Endócrinos/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Caracteres Sexuais , Glândula Tireoide/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra , Peixe-Zebra/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Glândula Tireoide/metabolismo , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
In recent years, the adverse effects of cadmium (Cd2+) on aquatic systems have attracted much attention because Cd2+ can induce endocrine disorders and toxicity in aquatic organisms at low levels. However, its effects on the thyroid system in native fish in Lhasa are still unclear. In the present study, Schizopygopsis younghusbandi larvae were exposed to Cd2+ (0.25, 2.5, 25 or 250 µg/L) for 7 or 14 days to determine its toxic effects on thyroid function. The results showed that whole-body total T4 and T3 levels were significantly decreased, which was accompanied by the significant upregulation of the expression of the dio1 and dio2 genes after exposure to Cd2+ for 7 or 14 days. Genes related to thyroid hormone synthesis (crh and tshß) were upregulated after both 7 and 14 days of Cd2+ exposure, possibly due to the negative feedback regulation of the hypothalamic-pituitary-thyroid (HPT) axis caused by a decrease in thyroid hormone. In addition, survival rates and body lengths were reduced after treatment with Cd2+. This suggests that Cd2+ caused developmental toxicity in Schizopygopsis younghusbandi larvae. An integrated assessment of biomarker response (IBR) showed that there were dose-dependent and time-dependent effects of Cd2+ exposure on Schizopygopsis younghusbandi larvae. Schizopygopsis younghusbandi larvae were sensitive to Cd2+, which caused adverse effects at a concentration as low as 2.5 µg/L. In summary, the results indicated that Cd2+ causes thyroid disruption and developmental toxicity in Schizopygopsis younghusbandi larvae and that wild Schizopygopsis younghusbandi larvae living in the Lhasa River are at potential ecological risk.
Assuntos
Cádmio/toxicidade , Cyprinidae/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipotálamo/patologia , Larva/efeitos dos fármacos , Hipófise/patologia , Glândula Tireoide/patologia , Animais , Hipotálamo/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacosRESUMO
1,1-Trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethane (o,p'-DDT) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) cause thyroid disruption, but the underlying mechanisms of these disturbances in fish remain unclear. To explore the potential mechanisms of thyroid dysfunction caused by o,p'-DDT and p,p'-DDE, thyroid hormone and gene expression levels in the hypothalamic-pituitary-thyroid (HPT) axis were measured, and the developmental toxicity were recorded in zebrafish larvae. Zebrafish embryos/larvae were exposed to o,p'-DDT (0, 0.28, 2.8, and 28 nM; or 0, 0.1, 1, and 10 µg/L) and p,p'-DDE (0, 1.57, 15.7, and 157 nM; or 0, 0.5, 5, and 50 µg/L) for 7 days. The genes related to thyroid hormone synthesis (crh, tshß, tg, nis and tpo) and thyroid development (nkx2.1 and pax8) were up-regulated in both the o,p'-DDT and p,p'-DDE exposure groups. Zebrafish embryos/larvae exposed to o,p'-DDT showed significantly increased total whole-body T4 and T3 levels, with the expression of ugt1ab and dio3 being significantly down-regulated. However, the p,p'-DDE exposure groups showed significantly lowered whole-body total T4 and T3 levels, which were associated with up-regulation and down-regulation expression of the expression of dio2 and ugt1ab, respectively. Interestingly, the ratio of T3 to T4 was significantly decreased in the o,p'-DDT (28 nM) and p,p'-DDE (157 nM) exposure groups, suggesting an impairment of thyroid function. In addition, reduced survival rates and body lengths and increased malformation rates were recorded after treatment with either o,p'-DDT or p,p'-DDE. In summary, our study indicates that the disruption of thyroid states was different in response to o,p'-DDT and p,p'-DDE exposure in zebrafish larvae.