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1.
Ecotoxicol Environ Saf ; 217: 112225, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33864983

RESUMO

Long-term exposure to excessive fluoride causes chronic damage in the body tissues and could lead to skeletal and dental fluorosis. Cartilage damage caused by excessive fluoride intake has gained wide attention, but how fluoride accumulation blocks the development of chondrocytes is still unclear. Here, we report a negative correlation between the length and growth plate width after NaF treatments via apoptosis and autophagy, with shrinkage of cells, nuclear retraction, dissolution of chondrocytes. Whereas, fluoride exposure had no significant effect on the number and distribution of the osteoclasts which were well aligned. More importantly, fluoride exposure induced apoptosis of tibial bone through CytC/Bcl-2/P53 pathways via targeting Caspase3, Caspase9, Bak1, and Bax expressions. Meanwhile, the Beclin1, mTOR, Pakin, Pink, and p62 were elevated in NaF treatment group, which indicated that long-term excessive fluoride triggered the autophagy in the tibial bone and produced the chondrocyte injury. Altogether, fluoride exposure induced the chondrocyte injury by regulating the autophagy and apoptosis in the tibial bone of ducks, which demonstrates that fluoride exposure is a risk factor for cartilage development. These findings revealed the essential role of CytC/Bcl-2/P53 pathways in long-term exposure to fluoride pollution and block the development of chondrocytes in ducks, and CytC/Bcl-2/P53 can be targeted to prevent fluoride induced chondrocyte injury.


Assuntos
Condrócitos/fisiologia , Patos/fisiologia , Fluoretos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Condrócitos/efeitos dos fármacos , Condrogênese , Fluoretos/metabolismo , Lâmina de Crescimento
2.
Chemosphere ; 277: 130222, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33794430

RESUMO

Fluorine (F) and its compounds produced from industrial production and coal combustion can cause air, water and soil contamination, which can accumulate in animals, plants and humans via food chain threatening public health. Fluoride exposure affects liver, kidney, gastrointestinal and reproductive system in humans and animals. Literature regarding fluoride influence on intestinal structure and microbiota composition in ducks is scarce. This study was designed to investigate these effects by using simple and electron microscopy and 16S rRNA sequencing techniques. Results indicated an impaired structure with reduced relative distribution of goblet cells in the fluoride exposed group. Moreover, the gut microbiota showed a significant decrease in alpha diversity. Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in both control and fluoride-exposed groups. Specifically, fluoride exposure resulted in a significant decrease in the relative abundance of 9 bacterial phyla and 15 bacterial genera. Among them, 4 phyla (Latescibacteria, Dependentiae, Zixibacteria and Fibrobacteres) and 4 genera (Thauera, Hydrogenophaga, Reyranella and Arenimonas) weren't even detectable in the gut microbiota of the ducks. In summary, higher fluoride exposure can significantly damage the intestinal structure and gut microbial composition in ducks.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Patos , Fluoretos/toxicidade , Humanos , RNA Ribossômico 16S/genética
3.
Aquat Toxicol ; 233: 105789, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33667915

RESUMO

Fluoride has been found to cause detrimental effects on fish gills. Despite essential roles in various metabolism activities, whether and how miRNAs participate in the course of toxicity caused by fluoride in gills is still unclear. In this study, male zebrafish were exposed to 0, 20, 40 mg/L fluoride for 60 days to study the underlying osmotic regulatory mechanism by determining the influences of fluoride on the miRNAs and regulated genes in gills. mRNAs were isolated from the gills and the expression profiles were analyzed by using Illumina Hiseq 2500 platforms. Expressions of 7 differentially miRNAs and some related-genes in gills were validated by qRT-PCR. The results showed that miRNAs expressions were notably altered by fluoride. A total of 584 and 327 miRNAs were remarkably changed after 20 and 40 mg/L fluoride exposure, of which 322 were increased and 262 were decreased in 20 mg/L fluoride group, whereas 219 were elevated and 108 were reduced in 40 mg/L fluoride group. The differentially expressive miRNAs confirmed by qRT-PCR were consistent with micro-assay data. Cluster of Orthologous Groups of proteins (COG) function classification showed that the target genes of differentially expressive miRNAs are mainly related to signal transduction mechanisms, replication, transcription, inorganic ion transport and metabolism, repair and recombination, and energy formation and transformation. In addition, fluoride disturbed the expressions of target genes involved in the osmoregulation of the gill in the fluoride-exposed zebrafish, such as the increased expressions of OSTF1 and the decreased expressions of Na+-K+-ATPase, CFTR, and AQP-3, which provides a possibility that miRNAs regulation induced by fluoride has an effects on osmotic regulation, providing new hints to the osmotic regulatory mechanism of the toxicity caused by fluoride in zebrafish, and distinguishes new biomarkers of miRNAs for fluoride toxicity.


Assuntos
Fluoretos/toxicidade , Expressão Gênica/efeitos dos fármacos , Brânquias/efeitos dos fármacos , MicroRNAs/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Brânquias/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , MicroRNAs/genética , Peixe-Zebra/genética
4.
Arch Oral Biol ; 125: 105093, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33667956

RESUMO

OBJECTIVES: The present study aimed to investigated the effect and mechanism of Ca2+ treatment on fluoride in ameloblast-lineage cells (ALCs). MATERIALS AND METHODS: The effects of fluoride and different Ca2+ levels treatment on the proliferative activity, cell apoptosis, cell cycle, intracellular free Ca2+, were firstly determined. Kallikrein 4 (KLK4), glucose-responsive protein 78 (GRP78), Protein kinase R -like endoplasmic reticulum kinase (PERK), the α subunit of eukaryotic initiation factor 2 (eIF2α), activating transcription factor 4 (ATF4), CCAAT enhancer-binding protein homologous protein (CHOP), were investigated in ALCs. RESULTS: The proliferative activity was obviously inhibited under concentrations of single fluoride high than 1 mM, and indicated highest proliferation at single 2.5 mM Ca2+ concentration in ALC cells. In addition, we found that single fluoride markedly induced intracellular free Ca2+ increasing, G2/M phase arrest, apoptosis. GRP78 and endoplasmic reticulum stress pathway of PERK/eIF2α/ATF4/CHOP were significantly increased, while the proliferation and KLK4 were markedly reduced in ALCs. Ca2+ additional treatment can obviously reverse the effect of fluoride-induced apoptosis and inhibition of KLK4. The effect of GRP78 and endoplasmic reticulum stress pathway of PERK/eIF2α/ATF4/CHOP were also alleviated under Ca2+ additional treatment in ALCs. More important, the results of 2.5 mmol/L Ca2+ treatment on the proliferation, cell cycle and apoptosis suggest this concentration is relatively better to mediate the intracellular Ca2+ homeostasis in ALCs. CONCLUSIONS: In sum, Ca2+-supplementation exerts antagonistic the toxic effects on fluoride and this inhibitory effect suggests the potential implications for Ca2+-supplementation on fluorosis.


Assuntos
Fator 4 Ativador da Transcrição , Fator de Iniciação 2 em Eucariotos , Fator 4 Ativador da Transcrição/metabolismo , Ameloblastos/metabolismo , Apoptose , Cálcio , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Fluoretos/toxicidade , Calicreínas , Transdução de Sinais , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo
5.
Mutat Res ; 861-862: 503297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33551106

RESUMO

Excess fluoride in water can produce changes in tooth enamel mineralization and lead to diseases such as dental or skeletal fluorosis. The present study aimed to assess the genotoxic effects, oxidative stress, and osteoblastic mineralization induced by fluorosilicic acid (FA) in murine bone marrow-derived mesenchymal stem cells (BM-MSCs). BM-MSCs were isolated from the femurs and tibias of rats and cultured under standard conditions. Cells exposure occurred for 3, 7, 14, and 21 days to different concentrations of FA (0.6-9.6 mg/L). Cytotoxicity was observed in 14 and 21 days of exposure for all concentrations of FA (cell proliferation below 60%), and for 3 and 7 days, in which the proliferation was above 80%. Alkaline comet assay results demonstrated significant increased damage at concentrations of 0.3-2.4 mg/L, and the micronucleus test showed increased rates for micronucleus (1.2-2.4 mg/L) and nuclear buds (NBUDs) (0.3-2.4 mg/L) (P < 0.05/Dunnett's test). An alkaline comet assay modified by repair endonuclease (FPG) was used to detect oxidized nucleobases, which occurred at 0.6 mg/L. The oxidative stress was evaluated by lipid peroxidation (TBARS) and antioxidant activity (TAC). Only lipid peroxidation was increased at concentrations of 0.6 mg/L and 1.2 mg/L (P < 0.001/Tukey's test). The osteogenesis process determined the level of extracellular matrix mineralization. The mean concentration of Alizarin red increased significantly in 14 days at the 0.6 mg/L concentration group (P < 0.05/Tukey's test) compared to the control group, and a significant difference between the groups regarding the activity of alkaline phosphatase (ALP) was observed. Unlike other studies, our results indicated that FA in BM-MSCs at concentrations used in drinking water induced genotoxicity, oxidative stress, and acceleration of bone mineralization.


Assuntos
Medula Óssea/patologia , Dano ao DNA , Fluoretos/toxicidade , Células-Tronco Mesenquimais/patologia , Estresse Oxidativo/efeitos dos fármacos , Ácido Silícico/toxicidade , Animais , Medula Óssea/efeitos dos fármacos , Diferenciação Celular , Células Cultivadas , Peroxidação de Lipídeos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Ratos , Ratos Endogâmicos WKY
6.
Ecotoxicol Environ Saf ; 208: 111548, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396092

RESUMO

In order to understand the pollution status of groundwater with geochemical evolution and appraisal of its probable public health risk due to nitrate (NO3-) and fluoride (F-), a total of 93 groundwater samples were collected during pre-monsoon (May) period from Wardha sub-basin, central India. By employing Piper plot, transition from Ca-HCO3 type water (recharge waters) to Na-Cl (saline water) type water through mixed Ca-Na-HCO3, mixed Ca-Mg-Cl (reverse ion exchange waters) and Ca-Cl types (leachate waters), were observed. The Geogenic processes such as silicate, dolomite, halite and carbonate weathering along with calcite precipitation and ion exchange process were identified as major controlling factors for evolution and alteration of groundwater chemistry. The Saturation index highlighted that the groundwater in the area is oversaturated with respect to the mineral calcite and dolomite, and under saturated with gypsum, fluorite and halite. The high NO3- and F- concentration overpassing the permissible limit were found in 54.8% and 18.5% of samples. The plot of F- with Na+/Ca2+, Na+/Mg2+ and F-/Cl- established fluoride bearing rock weathering is responsible for F- contamination. Based on the cluster analysis, the groundwater was grouped into Cluster-I Ca-Na-HCO3 type (61.3%) and Cluster-II Na-Ca-HCO3-Cl type (30.1%). The total hazard index (HI) based on human health risk assessment (HHRA) model for cumulative NO3- and F- toxicity through oral and dermal pathways were computed as 100%, 97.85% and 96.77% for children, female and male populations respectively. The HQ(nitrate) > 1 through ingestion pathway were in 84.95%, 68.82% and 62.37%, and HQ(fluoride) > 1 in 83.87%, 62.37% and 43.01% of the groundwater samples were recorded for children, female and male population respectively. The risk assessment study highlighted very high toxicity and severe health impact of ingestion of contaminated groundwater on public health.


Assuntos
Monitoramento Ambiental , Fluoretos/toxicidade , Nitratos/toxicidade , Poluentes Químicos da Água/toxicidade , Carbonato de Cálcio , Carbonatos , Criança , Feminino , Fluoretos/análise , Água Subterrânea/análise , Água Subterrânea/química , Humanos , Índia , Troca Iônica , Magnésio , Nitratos/análise , Medição de Risco , Poluentes Químicos da Água/análise
7.
Ecotoxicol Environ Saf ; 210: 111876, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33418158

RESUMO

Evidence has shown that miRNAs could play a role in dental fluorosis, but there is no study has investigated the global expression miRNA profiles of fluoride-exposed enamel organ. In this study, we analysed the differentially expressed (DE) miRNAs between fluoride-treated and control enamel organ for the first time and found several candidate miRNAs and signaling pathways worthy of further research. Thirty Wistar rats were randomly distributed into three groups and exposed to drinking water with different fluoride contents for 10 weeks and during the gestation. The three groups were a control group (distilled water), medium fluoride group (75 mg/L NaF), and high fluoride group (150 mg/L NaF). On the embryonic day 19.5, the mandible was dissected for histological analysis, and the enamel organ of the mandibular first molar tooth germ was collected for miRNA sequencing (miRNA-seq) and quantitative real-time PCR analysis (qRT-PCR). Typical dental fluorosis was observed in the incisors of the prepregnant rats. In addition to the disorganized structure of enamel organ cells, 39 DE miRNAs were identified in the fluoride groups compared with the control group, and good agreement between the miRNA-seq data and qRT-PCR data was found. The functional annotation of the target genes of 39 DE miRNAs showed significant enrichment in metabolic process, cell differentiation, calcium signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway terms. This study provides a theoretical reference for an extensive understanding of the mechanism of fluorosis and potential valuable miRNAs as therapeutic targets in fluorosis.


Assuntos
Órgão do Esmalte/efeitos dos fármacos , Fluoretos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , MicroRNAs , Animais , Embrião de Mamíferos , Órgão do Esmalte/embriologia , Órgão do Esmalte/metabolismo , Feminino , Fluorose Dentária , Ratos Wistar , Transcriptoma/efeitos dos fármacos
8.
Chemosphere ; 273: 129607, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33508686

RESUMO

Gastrointestinal signs and symptoms are the first signs of toxicity due to exposure to fluoride (F). This suggests the possibility that lower levels of subchronic F exposure may affect the gut. The aim of this study was to evaluate changes in the morphology, proteome and microbiome of the ileum of rats, after subchronic exposure to F. Male rats ingested water with 0, 10, or 50 mgF/L for thirty days. Treatment with F, regardless of the dose, significantly decreased the density of HuC/D-IR neurons, whereas CGRP-IR and SP-IR varicosities were significantly increased compared to the control group. Increased VIP-IR varicosities were significantly increased only in the group treated with 50 mgF/L. A significant increase in thickness of the tunica muscularis, as well as in the total thickness of the ileum wall was observed at both F doses when compared to controls. In proteomics analysis, myosin isoforms were increased, and Gastrotopin was decreased in F-exposed mice. In the microbiome metagenomics analysis, Class Clostridia was significantly reduced upon exposure to 10 mgF/L. At the higher F dose of 50 mg/L, genus Ureaplasma was significantly reduced in comparison with controls. Morphological and proteomics alterations induced by F were marked by changes associated with inflammation, and alterations in the gut microbiome. Further studies are needed to determine whether F exposure increases inflammation with secondary effects of the gut microbiome, and/or whether primary effects of F on the gut microbiome enhance changes associated with inflammation.


Assuntos
Fluoretos , Microbioma Gastrointestinal , Animais , Firmicutes , Fluoretos/toxicidade , Masculino , Camundongos , Proteoma , Proteômica , Ratos
9.
Chemosphere ; 262: 127891, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32799150

RESUMO

Fluoride generally exists in the natural environment, and has been reported to induce serious environmental hazard to animals, plants, and even humans via ecological cycle. Silkworm, Bombyx mori, which showed significant growth and reproductivity reduction when exposed to fluoride, has become a model to evaluate the toxicity of fluoride. However, the detailed mechanism underlying fluoride toxicity and corresponding transport proteins remain unclear. In this study, we performed RNA-seq of the larval midgut and fat body with fluoride exposure and normal treatment. Differential analysis showed that there were 4405 differentially expressed genes in fat body and 4430 DEGs in midgut with fluoride stress. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we identified several key pathways involved in the fluoride exposure and poisoning. We focused on the oxidative phosphorylation and MAPK signal pathway. QRT-PCR confirmed that oxidative phosphorylation process was remarkably inhibited by fluoride exposure and resulted in the blocking of ATP synthesis. The MAPK signal pathway was stimulated via phosphorylation signal transduction. Moreover, by protein structure analysis combined with the DEGs, we screen 36 potential membrane proteins which might take part in transporting fluoride. Taken together, the results of our study expanded the underlying mechanisms of fluoride poisoning on silkworm larval growth and development, and implied potential fluoride transport proteins in silkworm.


Assuntos
Bombyx/fisiologia , Fluoretos/toxicidade , Substâncias Perigosas/toxicidade , Tecido Adiposo/metabolismo , Animais , Bombyx/metabolismo , Sistema Digestório/metabolismo , Corpo Adiposo/metabolismo , Perfilação da Expressão Gênica/métodos , Inativação Metabólica , Larva/genética , Transcriptoma/fisiologia
10.
Chemosphere ; 262: 127826, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182120

RESUMO

The present manuscript investigates the roles of silicon nanoparticles (SiNPs) in ameliorating fluoride toxicity in the susceptible rice cultivar, IR-64. Fluoride toxicity reduced overall growth and yield by suppressing grain development. Fluoride stress alarmingly increased the accumulation of cobalt, which together with fluoride triggered electrolyte leakage, malondialdehyde, methylglyoxal and hydrogen peroxide accumulation and NADPH oxidase activity. The overall photosynthesis was compromised due to chlorosis and inhibited Hill activity. Nano-Si-priming efficiently ameliorated molecular injuries and restored yield by reducing fluoride bioaccumulation particularly in the grains. The level of non-enzymatic antioxidants like anthocyanins, flavonoids, phenolics and glutathione was stimulated upon SiNP-priming. Nano-Si-pulsing removed fluoride-mediated inhibition of glutathione synthesis by activating glutathione reductase. Glutathione was utilized to activate glyoxalases and associated enzymes like glutathione-S-transferase and glutathione peroxidase. Uptake of nutrients like silicon, potassium, zinc, copper, iron, nickel, manganese, selenium and vanadium improved seedling health even during prolonged fluoride stress. Nano-Si-pulsing produced a nanozymatic effect, since high level of crucial co-factors like copper, zinc and iron stimulated the activity of superoxide dismutase, catalase, ascorbate peroxidase and guaiacol peroxidase, which synergistically with other enzymatic and non-enzymatic antioxidants scavenged reactive oxygen species and promoted fluoride tolerance. Overall, the study supported by statistical modelling using principal component analysis, t-distributed stochastic neighbour embedding and multidimensional scaling, established the potential of SiNP to promote safe rice cultivation and precision farming even in fluoride-infested environments.


Assuntos
Fluoretos/toxicidade , Oryza/fisiologia , Silício/química , Poluentes Químicos da Água/toxicidade , Antioxidantes/metabolismo , Ascorbato Peroxidases , Catalase , Glutationa/metabolismo , Glutationa Peroxidase , Peróxido de Hidrogênio/metabolismo , Malondialdeído , Oryza/efeitos dos fármacos , Peroxidase , Espécies Reativas de Oxigênio/metabolismo , Plântula/efeitos dos fármacos , Superóxido Dismutase
11.
Ecotoxicol Environ Saf ; 209: 111826, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360592

RESUMO

BACKGROUND: Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear. OBJECTIVES: We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water. METHODS: We recruited 567 resident children, aged 6-11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment. RESULTS: In adjusted model, fluoride exposure was inversely associated with IQ scores (ß = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). CONCLUSIONS: Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.


Assuntos
Dopamina/genética , Exposição Ambiental/estatística & dados numéricos , Fluoretos/toxicidade , Inteligência/efeitos dos fármacos , Criança , China/epidemiologia , Estudos Transversais , Água Potável , Feminino , Fluoretos/análise , Genótipo , Humanos , Testes de Inteligência , Masculino , Polimorfismo Genético
12.
Ecotoxicol Environ Saf ; 209: 111732, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33373928

RESUMO

Fluoride, widely presented in drinking water and tea, may be detrimental or beneficial to the human health, depending on its dosages ingested. However, the relationship of different dosages of fluoride and gut microbiota is still unclear. In this work, the fermentation model using fecal samples provided by four volunteers was used to evaluate the effects of different dosages of fluoride (1, 2, 10 and 15 mg/L) on the gut microbiota in vitro. The result showed low dosages of fluoride (1 and 2 mg/L) had limited effect on the structure and functional Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of gut microbiota. Furthermore, the low dosage of fluoride could promote the growth of beneficial gut microbiota, including Faecalibacterium and Lactobacillus. Whereas, the high dosage of fluoride (10 and 15 mg/L) significantly changed the composition and functional KEGG pathway of gut microbiota. Moreover, the high dosage of fluoride could also reduce the beneficial gut microbiota, including Faecalibacterium and Phascolarctobacterium, and increase the harmful bacterium including Proteobacteria and Enterobacteriaceae. Both low and high dosages of fluoride showed limited effect on the productions of short-chain fatty acids (SCFAs). Thus, the beneficial or detrimental fluoride to gut microbiota depends on its dosages. The fluoride is expected to serve as a food additive in suitable dosage to improve human health through modulation of the gut microbiota. Moreover, more attention should be paid to toxicity of fluoride with high dosage to gut microbiota.


Assuntos
Fluoretos/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Bactérias/metabolismo , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fermentação , Fluoretos/análise , Humanos , Lactobacillus/metabolismo
13.
Ecotoxicol Environ Saf ; 203: 111031, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888610

RESUMO

Bone mineral density (BMD) changes were reported to be associated with excessive fluoride exposure and abnormal expression of RUNX2. However, whether the alteration of methylation status, a most commonly used marker for the alteration of gene expression in epidemiological investigation, of RUNX2 is associated with low-to-moderate fluoride exposure and BMD changes has not been reported. Our study aims to explore the role of RUNX2 promoter methylation in BMD changes induced by low-to-moderate fluoride exposure. A total of 1124 adults (413 men and 711 women) were recruited from Kaifeng City in 2017. We measured BMD using ultrasound bone densitometer. Concentrations of urinary fluoride (UF) were measured using ion-selective electrode, and the participants were grouped into control group (CG) and excessive fluoride group (EFG) according to the concentration of UF. We extracted DNA from fasting peripheral blood samples and then detected the promoter methylation levels of RUNX2 using quantitative methylation-specific PCR. Relationships between UF concentration, RUNX2 promoter methylation and BMD changes were analyzed using generalized linear model and logistic regression. Results showed in EFG (UF concentration > 1.6 mg/L), BMD was negatively correlated with UF concentration (ß: -0.14; 95%CI: -0.26, -0.01) and RUNX2 promoter methylation (ß: -0.13; 95%CI: -0.22, -0.03) in women. The methylation rate of RUNX2 promoter increased by 2.16% for each 1 mg/L increment in UF concentration of women in EFG (95%CI: 0.37, 3.96). No any significant associations between UF concentration, RUNX2 promoter methylation, and BMD were observed in the individuals in CG. Mediation analysis showed that RUNX2 promoter methylation mediated 18.2% (95% CI: 4.2%, 53.2%) of the association between UF concentration and BMD of women in EFG. In conclusion, excessive fluoride exposure (>1.6 mg/L) is associated with changes of BMD in women, and this association is mediated by RUNX2 promoter methylation.


Assuntos
Densidade Óssea/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Exposição Ambiental/análise , Fluoretos/toxicidade , Poluentes Químicos da Água/toxicidade , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea/genética , China , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Estudos Transversais , Metilação de DNA/efeitos dos fármacos , Feminino , Fluoretos/urina , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Inquéritos e Questionários , Poluentes Químicos da Água/urina
14.
Chemosphere ; 258: 127387, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947680

RESUMO

It is well known that serum is an ideal and potential choice to reflect the toxicity of fluoride. However, the effects of fluoride on serum metabolome have not been reported until now. In this study, the models of 3-week-old rats exposed fluoride by breast milk and 11-week-old rats exposed fluoride via breast milk and drinking water containing sodium fluoride (100 mg/L) were established. Using Ultra Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (UPLC-MS/MS), as compared with control group, 28 negative (NEG) and 52 positive (POS) metabolites were significantly up-regulated, meanwhile 30 NEG and 21 POS significantly down-regulated metabolites were found in serum of 3-week-old rats exposed to fluoride. For 11-week-old fluorosis rats, there were 119 NEG and 65 POS metabolites significantly increased, and 7 NEG, 5 POS metabolites were obviously decreased. Importantly, nicotinamide, adenosine, 1-Oleoyl-sn-glycero-3-phosphocholine (OGPC), and 1-Stearoyl-sn-glycerol 3-phosphocholine (SGPC) were shared by two models. The metabolites of urea cycle, such as urea and N2-Acetyl-l-ornithine, betaine as a methyl donor, were regarded to reflect the fluorosis degree. These metabolites could be the potential markers of fluorosis, contributing to the prevention and treatment of fluorosis.


Assuntos
Fluoretos/toxicidade , Metaboloma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Betaína , Cromatografia Líquida , Água Potável/química , Feminino , Humanos , Masculino , Metabolômica , Leite/metabolismo , Ratos , Fluoreto de Sódio , Espectrometria de Massas em Tandem
15.
Ecotoxicol Environ Saf ; 204: 111058, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32739676

RESUMO

Skeletal fluorosis causes growth plate impairment and growth retardation during bone development. However, the mechanism of how fluoride impairs chondrocyte is unclear. To explore the effect of fluoride on chondrocyte differentiation and the regulation of circadian clock signaling pathway during chondrogenesis, we treated ATDC5 cells with fluoride and carried out a series of experiments. 10-3 M fluoride inhibited cell viability and significantly decreased the expression of Sox9 and Col2a1 (P < 0.05). Fluoride inhibited proteoglycan synthesis and decreased significantly the expression of Aggrecan, Ihh and Col10a1 (P < 0.05). Meanwhile, fluoride significantly inhibited the expression of Bmal1 and disrupted circadian clock signaling pathway (P < 0.05). Furthermore, fluoride disrupted the time-dependent expression of circadian clock molecules and stage-specific differentiation markers. Overexpression of Bmal1 by lentivirus reversed the adverse effects of fluoride on chondrogenesis. These results suggested that fluoride inhibited chondrocyte viability and delayed chondrocyte differentiation. Fluoride delayed chondrogenesis partly via interfering with Bmal1 and circadian clock signaling pathway. Nevertheless, the specific mechanism of circadian clock in fluoride-induced cartilage damage needs to be further studied.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Relógios Circadianos , Poluentes Ambientais/toxicidade , Fluoretos/toxicidade , Animais , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese/fisiologia , Colágeno Tipo X/genética , Colágeno Tipo X/metabolismo , Lâmina de Crescimento/efeitos dos fármacos , Lâmina de Crescimento/metabolismo , Camundongos , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Transdução de Sinais
16.
Ecotoxicol Environ Saf ; 202: 110962, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800233

RESUMO

Chronic exposure to fluoride (F) beyond the permissible limit (1.5 ppm) is known to cause detrimental health effects by induction of oxidative stress-mediated DNA damage overpowering the DNA repair machinery. In the present study, we assessed F induced oxidative stress through monitoring biochemical parameters and looked into the effect of chronic F exposure on two crucial DNA repair genes Ogg1 and Rad51 having important role against ROS induced DNA damages. To address this issue, we exposed Swiss albino mice to an environmentally relevant concentration of fluoride (15 ppm NaF) for 8 months. Results revealed histoarchitectural damages in liver, brain, kidney and spleen. Depletion of GSH, increase in lipid peroxidation and catalase activity in liver and brain confirmed the generation of oxidative stress. qRT-PCR result showed that expressions of Ogg1 and Rad51 were altered after F exposure in the affected organs. Promoter hypermethylation was associated with the downregulation of Rad51. F-induced DNA damage and the compromised DNA repair machinery triggered intrinsic pathway of apoptosis in liver and brain. The present study indicates the possible association of epigenetic regulation with F induced neurotoxicity.


Assuntos
Dano ao DNA , DNA Glicosilases/genética , Reparo do DNA , Epigênese Genética/efeitos dos fármacos , Fluoretos/toxicidade , Rad51 Recombinase/genética , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos
17.
Chemosphere ; 260: 127565, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32758781

RESUMO

The effects of fluoride on endocrine tissues has not been sufficiently explored to date. The current body of knowledge suggest significant effects of that mineral on reducing sex hormone levels, which may consequently impair fertility and disrupt puberty. The majority of studies confirm that sodium fluoride increases TSH levels and decreases the concentrations of T3 and T4 produced by the thyroid. Moreover, a correlation was observed between NaF and increased secretion of PTH by the parathyroid glands, without a significant impact on body calcium levels. Probably, fluoride may exert adverse effects on insulin levels, impairing pancreatic function and resulting in abnormal glucose tolerance. Observations also include decreased levels of cortisol secreted by the adrenal glands. In light of the few existing studies, the mechanism of fluoride toxicity on the endocrine system has been described.


Assuntos
Sistema Endócrino/efeitos dos fármacos , Fluoretos/farmacologia , Glândulas Suprarrenais/metabolismo , Animais , Fluoretos/efeitos adversos , Fluoretos/toxicidade , Humanos , Hidrocortisona/metabolismo , Insulina/análise , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo , Fluoreto de Sódio/farmacologia , Fluoreto de Sódio/toxicidade , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo
18.
Ecotoxicol Environ Saf ; 203: 110951, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32678752

RESUMO

The growing use of rare-earth doped upconversion nanoparticles (UCNPs) has caused increasing concern about their biosafety. Here, to understand the toxicity of UCNPs and their mechanism in HepG2 cells, we systematically study the cytotoxicity, uptake and elimination behaviors of three types of UCNPs combined multiple cytotoxicity evaluation means with inductively coupled plasma mass spectrometry (ICP-MS) detection. Sodium yttrium fluoride, doped with 18% (molar ratio) ytterbium and 2% erbium (NaYF4: Yb3+, Er3+) was selected as the model UCNPs with two sizes (35 and 55 nm), and the poly(acrylic acid) and polyethylenimine were selected as the representatives of negative and positive surface coating of UCNPs, respectively. UCNPs were found to induce cytotoxicity in time- and dose-dependent manners, which might be mediated by reactive oxygen species generation and oxidative stress. Apoptosis, inflammation, and metabolic process were enhanced after cells exposed to 200 mg/L UCNPs for 48 h. Increase in the protein levels of cleaved caspased-9, cleaved caspase-3 and Bax and decrease in the anti-apoptotic protein, Bcl-2 suggested that the mitochondria mediated pathway was involved in UCNP-induced apoptosis. With the aid of ICP-MS, it demonstrated that the cytotoxicity was associated with internalized amount of UCNPs, which largely relied on their surface properties rather than size in the tested range. By comparing UCNPs with Y3+ ions, it demonstrated that NPs properties played a nonnegligible role in the cytotoxicity of UCNPs. These findings provide new insights for fundamental understanding of cytotoxicity of UCNPs and may contribute to more rational use of these materials in the future.


Assuntos
Endocitose/efeitos dos fármacos , Érbio/toxicidade , Fluoretos/toxicidade , Nanopartículas/toxicidade , Itérbio/toxicidade , Ítrio/toxicidade , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Sobrevivência Celular , Érbio/química , Érbio/metabolismo , Fluoretos/química , Fluoretos/metabolismo , Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Propriedades de Superfície , Itérbio/química , Itérbio/metabolismo , Ítrio/química , Ítrio/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-32525728

RESUMO

Groundwater is a major source of drinking water for millions of people around the world. Over 400 million people in Africa depend solely on it as their main source of water supply. Fluoride is a common contaminant in groundwater. In low concentration (0.5-1.0 mg/L), fluoride is needed by humans for healthy development of bones and teeth, however, a concentration >1.5 mg/L has been linked with several fluorosis and non-fluorosis diseases. Dental and skeletal fluorosis are the major fluorosis diseases commonly reported with the consumption of fluoride-rich water. Although fluoride intake through other pathways such as the drinking of tea and eating of vegetables have been reported, the drinking of fluoride-rich water remains the major pathway of fluoride into humans. Cases of high fluoride levels in groundwater have been reported in almost all the sub-Saharan Africa region but it is more prevalent in East African countries, Sudan and South Africa. Although fluoride is present in surface water mostly in the East African Rift Valley across different countries in East Africa, its significant or high levels are usually associated with groundwater. Geogenic sources such as fluorite, apatite, biotite, amphibole, micas, topaz, cryolite, muscovite and fluorspar have been identified as the major sources of fluoride in groundwater. High fluoride levels have been reported across sub Saharan Africa, with generally higher levels in East Africa resulting from the volcanic activities in the rift system. Dental fluorosis has been reported in many sub-Saharan African countries including South Africa, Tanzania, Uganda, Ethiopia, Kenya, Sudan, Niger, Nigeria, Benin, Ghana and Malawi. Geothermal temperature has been regarded as one of the driving forces for high fluoride levels recorded in groundwater from deep aquifers and geothermal springs. The most affected people with the consumption of fluoride-rich water are the poor with low socioeconomic status who live in rural areas. Some of the proposed alternative sources include rainwater and fog water harvesting and blending of water from various sources. Low-cost and sustainable deflouridation technique remains one of the best ways to treat fluoride contaminated water either at communal level or at the point-of-use.


Assuntos
Fluoretos/toxicidade , Sedimentos Geológicos/química , Água Subterrânea/química , Poluentes Químicos da Água/toxicidade , Abastecimento de Água/métodos , África ao Sul do Saara/epidemiologia , Fluoretos/análise , Fluorose Dentária/epidemiologia , Fluorose Dentária/etiologia , Água Subterrânea/normas , Humanos , Prevalência , Poluentes Químicos da Água/análise , Abastecimento de Água/normas
20.
Chemosphere ; 256: 127105, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32450357

RESUMO

Previous studies have shown that waterborne fluoride exposure has adverse effects on the reproductive system of zebrafish. However, the underlying toxic mechanisms were still not clear. In the present study, female zebrafish were exposed to different concentrations of 0.787 (Control), 18.599, 36.832 mg/L of fluoride for 30 d and 60 d, and the effects of different doses of fluoride on ovary development, reproductive hormones, oogenesis, ROS content, antioxidant levels, and the expression of apoptosis-related genes and proteins in the ovaries of female zebrafish were analyzed. The results showed that ovarian weight and GSI were significantly decreased, FSH, LH and VTG levels were significantly reduced, the transcriptional profiles of oogenesis-related genes (tgfß1, bmp15, gdf9, mprα, mprß, ptg2ß) were remarkably altered, ROS levels was notably increased, the SOD, CAT, GPx activities and GSH content as well as their mRNA expressions were significantly decreased, MDA content was remarkably increased, the expressions of apoptosis-related genes and proteins (caspase3, caspase8, caspase9, Fas-L, Cytochrome C, Bax and Bcl-2) were significantly changed, the ratio of Bax/Bcl-2 protein levels were notably increased. Taken together, this study demonstrated that fluoride exposure significantly affected ovarian development, decreased the reproductive hormones, affected oogenesis, induced oxidative stress, caused apoptosis through both extrinsic and intrinsic pathways in ovary of zebrafish. Indicating that oogenesis, oxidative stress, and apoptosis were responsible for the impairment of ovarian development.


Assuntos
Fluoretos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Feminino , Oogênese/efeitos dos fármacos , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Diferenciação Sexual , Peixe-Zebra/metabolismo
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