RESUMO
Artisanal brick-making exposes workers to mixtures of environmental contaminants under precarious conditions. This study assessed exposure to PAHs, arsenic, fluoride, lead, and their associations with early kidney damage biomarkers in 109 adults from three brick-making communities in central Mexico. Urinary and blood concentrations of contaminants were measured using validated analytical methods, and renal biomarkers (CYS-C, B2M, OPN, KIM-1, NGAL) were quantified via multiplex ELISA. Median urinary concentrations of 1-OH-PYR (1.3-2.3 µmol/mol uCr), arsenic (20.8-45.3⯵g/L), and fluoride (1.6-2.6â¯mg/g uCr) exceeded reference values in a substantial proportion of participants. Cystatin-C and osteopontin showed significant associations with arsenic, fluoride, and PAH metabolites, including nonlinear relationships. No consistent associations were found for NGAL or KIM-1. These findings provide evidence of early renal alterations related to environmental exposures and support the utility of early-effect biomarkers for public health surveillance in vulnerable populations exposed to nephrotoxic mixtures under informal occupational conditions.
Assuntos
Poluentes Ambientais , Rim , Exposição Ocupacional , Humanos , Biomarcadores/urina , Biomarcadores/sangue , Adulto , México , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Masculino , Feminino , Pessoa de Meia-Idade , Hidrocarbonetos Policíclicos Aromáticos/urina , Hidrocarbonetos Policíclicos Aromáticos/sangue , Poluentes Ambientais/urina , Poluentes Ambientais/sangue , Receptor Celular 1 do Vírus da Hepatite A , Arsênio/urina , Arsênio/sangue , Fluoretos/urina , Fluoretos/sangue , Chumbo/urina , Chumbo/sangue , Adulto Jovem , Rim/efeitos dos fármacos , Exposição Ambiental , Cistatina C/sangue , Lipocalina-2/sangue , Materiais de ConstruçãoRESUMO
Dental fluorosis (DF) is a condition caused by prolonged fluoride (F) exposure during tooth development, leading to enamel changes. Clinically, it presents as opaque white spots and, in severe cases, striations, mottling, or enamel loss. Although chronic fluoride exposure is the main factor, severity does not always align with fluoride levels, suggesting genetic influences, such as variants in the DLX3, ESR1 and ESR2 genes, which regulate tooth development. This cross-sectional case-control study included 79 women from Durango, Mexico. The severity of dental fluorosis was assessed across the entire mouth via the Thylstrup-Fejerskov Index (TFI), with the highest score recorded for evaluation. The classification followed the World Health Organization (WHO) guidelines from Geneva, 1997, categorizing severity into mild, moderate, and severe groups. The fluoride concentrations in the water and urine were quantified via potentiometry. Genotyping was conducted via real-time PCR. The average concentration of fluoride (ppm) was 5.38(± 2.73 SD) for tap water, 4.79±(4.60 SD) for urine and 2.32(± 2.78 SD) for drinking water TFI followed the next distribution: 72.1% of the participants had moderate, 22.7% had mild, and 5.2% had severe fluorosis. A positive correlation between F in drinking water and F in urine. (0.46, p = 0.001) and a negative correlation between F in drinking water and the mean corpuscular volume (MCV) (-0.41, p = 0.01) was found. Additionally, a significant association was identified between the recessive model of the rs2278163 DLX3 and rs12154178 ESR1 polymorphisms and mild and moderate fluorosis (p = 0.02, OR = 0.25, 95% CI: 0.07-0.88 and p = 0.034, OR = 0.31, 95% CI: 0.10-0.95, respectively).
Assuntos
Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Fluoretos , Fluorose Dentária , Proteínas de Homeodomínio , Fatores de Transcrição , Humanos , Fluorose Dentária/genética , Fluorose Dentária/etiologia , México , Feminino , Estudos de Casos e Controles , Fluoretos/análise , Fluoretos/urina , Fluoretos/efeitos adversos , Adulto , Receptor alfa de Estrogênio/genética , Estudos Transversais , Fatores de Transcrição/genética , Proteínas de Homeodomínio/genética , Receptor beta de Estrogênio/genética , Pessoa de Meia-Idade , Água Potável/química , GenótipoRESUMO
BACKGROUND: Early-life lead exposure affects cognitive development and emerging evidence suggests similar effects of cadmium and fluoride. OBJECTIVE: To assess the impact of gestational and childhood exposure to lead, cadmium, and fluoride on cognitive abilities and behavioral and social communication problems. METHODS: We studied 470 pregnant women (gestational week 29) and their 4-year-old children from the NICE cohort in northern Sweden. Concentrations of erythrocyte lead and cadmium and urinary cadmium were measured using inductively coupled plasma mass spectrometry and urinary fluoride with an ion-selective electrode. Urinary concentrations were specific-gravity adjusted. Associations of log2-transformed exposure concentrations with cognitive abilities (full-scale IQ and verbal comprehension by Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition), behavioral problems (Child Behavior Checklist), and social communication (Social Responsiveness Scale-Second Edition) were evaluated with multivariable-adjusted linear regression analysis. RESULTS: Both gestational and cord erythrocyte lead concentrations were non-significantly inversely associated with child cognitive abilities (full-scale IQ: B [95%CI]: -1.2 [-2.9, 0.5] and -1.6 [-3.7, 0.4], respectively; per doubling of exposure). Similarly, both gestational and child urinary cadmium were inversely associated with cognitive abilities (full-scale IQ: -1.1 [-2.5, 0.3] and -1.1 [-2.5, 0.4], verbal comprehension: -1.2 [-3.1, 0.6] and -1.4 [-3.4, 0.6], respectively). Urinary fluoride concentrations showed no association with cognitive abilities. However, gestational fluoride was associated with increasing externalizing problems (0.9 [-0.3, 2.0]) and ADHD raw scores (0.3 [0.0, 0.6]). Childhood erythrocyte lead and urinary cadmium were non-significantly associated with increased behavioral problems (lead with total problems: 1.2 [-0.4, 2.9] and internalizing problems: 1.5 [-0.4, 3.4]; cadmium with externalizing problems: 1.1 [-0.2, 2.4]). CONCLUSION: Despite non-significant associations, both lead and cadmium exposure showed consistent inverse associations with cognitive abilities at 4 years, whereas associations with behavioral problems were less conclusive, especially for cadmium. Results on fluoride indicated association with externalizing problems, including ADHD, but prevalence of behavioral problems was low, increasing uncertainty.
Assuntos
Cádmio , Cognição , Fluoretos , Chumbo , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Pré-Escolar , Chumbo/sangue , Chumbo/urina , Fluoretos/urina , Fluoretos/efeitos adversos , Cádmio/urina , Cádmio/sangue , Gravidez , Cognição/efeitos dos fármacos , Suécia/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Masculino , Poluentes Ambientais/urina , Poluentes Ambientais/sangue , Exposição Ambiental/análise , Exposição Ambiental/efeitos adversos , Coorte de Nascimento , Estudos de Coortes , Comportamento Infantil/efeitos dos fármacos , AdultoRESUMO
The relationship between dental fluorosis and alterations in the salivary proteome remains inadequately elucidated. This study aimed to investigate the salivary proteome and fluoride concentrations in urine and drinking water among Thai individuals afflicted with severe dental fluorosis. Thirty-seven Thai schoolchildren, aged 6-16, were stratified based on Thylstrup and Fejerskov fluorosis index scores: 10 with scores ranging from 5 to 9 (SF) and 27 with a score of 0 (NF). Urinary and water fluoride levels were determined using an ion-selective fluoride electrode. Salivary proteomic profiling was conducted via LC-MS/MS, followed by comprehensive bioinformatic analysis. Results revealed significantly elevated urinary fluoride levels in the SF group (p = 0.007), whereas water fluoride levels did not significantly differ between the two cohorts. Both groups exhibited 104 detectable salivary proteins. The NF group demonstrated notable upregulation of LENG9, whereas the SF group displayed upregulation of LDHA, UBA1, S100A9, H4C3, and LCP1, all associated with the CFTR ion channel. Moreover, the NF group uniquely expressed 36 proteins, and Gene Ontology and pathway analyses suggested a link with various aspects of immune defense. In summary, the study hypothesized that the CFTR ion channel might play a predominant role in severe fluorosis and highlighted the depletion of immune-related salivary proteins, suggesting compromised immune defense in severe fluorosis. The utility of urinary fluoride might be a reliable indicator for assessing excessive fluoride exposure.
Assuntos
Fluoretos , Fluorose Dentária , Proteômica , Saliva , Fluorose Dentária/metabolismo , Humanos , Criança , Masculino , Saliva/metabolismo , Saliva/química , Feminino , Fluoretos/urina , Fluoretos/análise , Adolescente , Proteômica/métodos , Proteoma/análise , Tailândia , Proteínas e Peptídeos Salivares/metabolismo , Proteínas e Peptídeos Salivares/análise , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Espectrometria de Massas em Tandem , Água PotávelRESUMO
Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown. Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US. Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024. Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure. Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted. Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02). Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.
Assuntos
Fluoretos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Pré-Escolar , Fluoretos/urina , Fluoretos/efeitos adversos , Estudos Prospectivos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Masculino , Exposição Materna/efeitos adversos , Exposição Materna/estatística & dados numéricos , Desenvolvimento Infantil/efeitos dos fármacos , Comportamento Infantil/efeitos dos fármacos , Terceiro Trimestre da Gravidez/urina , Los Angeles/epidemiologiaRESUMO
PURPOSE: The purpose of the study was to determine the fluoride (F) and silver (Ag) ions levels in the saliva and urine of healthy children after silver diamine fluoride (SDF) application on dental carious lesions. METHODS: Sixty children (4-6 years with ≥ 3 caries lesions) were recruited from the outpatient department of Pediatric Dentistry. From each child, 3 ml unstimulated saliva samples were collected at baseline, one hour, and 24 h after SDF application. Similarly, 3 ml urine samples were collected prior to and after 24 h of SDF application. F and Ag ion concentrations were determined by fluoride ion-selective electrode (ISE) and inductively coupled plasma mass spectrometry (ICPMS), respectively. RESULTS: The mean ± standard deviation (SD) baseline, 1-h, and 24-h salivary F concentrations (ppm) were 0.07 ± 0.07, 0.93 ± 0.48, and 0.19 ± 0.19, respectively, while the mean baseline and 24-h urinary F concentrations (ppm) were 0.33 ± 0.20 ppm and 0.43 ± 0.25 ppm, respectively. The mean baseline, 1-h, and 24-h salivary Ag concentrations (ppb) were 4.22 ± 3.15, 4198 ± 350, and 56.93 ± 37, respectively. The mean baseline and 24-h urinary Ag concentrations (ppb) were 2.80 ± 2.93 ppb and 4.72 ± 4.0 ppb, respectively. There were statistically elevated F and Ag ion concentrations at 1 h and 24 h after SDF application as compared to the baseline. CONCLUSION: Salivary and urinary F and Ag ions concentrations elevated significantly at 24 h following SDF applications in children. A significant high recovery of these ions in urine indicates minimal systemic absorption, thus intermittent topical application of 38% SDF has a minimal risk of toxicity.
Assuntos
Fluoretos Tópicos , Fluoretos , Compostos de Amônio Quaternário , Saliva , Compostos de Prata , Prata , Humanos , Saliva/química , Fluoretos Tópicos/administração & dosagem , Criança , Pré-Escolar , Estudos Prospectivos , Feminino , Masculino , Fluoretos/análise , Fluoretos/urina , Compostos de Amônio Quaternário/análise , Compostos de Amônio Quaternário/administração & dosagem , Cárie Dentária , Cariostáticos/análise , Cariostáticos/administração & dosagem , Eletrodos Seletivos de ÍonsRESUMO
To investigate the relationship between fluoride exposure and Osteochondroma (OC) prevalence, a cross-sectional study was conducted in drinking water endemic fluorosis areas of Heilongjiang Province, China. Our study first reported that the prevalence of OC was 2.3% in drinking water endemic fluorosis areas of Heilongjiang Province, China, and no difference in gender. Logistic regression analysis found that compared to 1st quartile participants, the prevalence of OC was 73% lower in the 2nd quartile participants of WF (Water fluoride), and 3.4 times higher among the 2nd quartile UF (Urinary fluoride) participants. Our study suggests that 0.259-0.420 mg/L of WF may be considered an appropriate level for reducing OC prevalence, while UF (≥0.750 mg/L) could slightly increase the prevalence of OC. In summary, the link between fluoride and OC prevalence is complicated and needs to be further investigated in a cohort population.
Assuntos
Água Potável , Fluoretos , Osteocondroma , Humanos , China/epidemiologia , Estudos Transversais , Masculino , Fluoretos/análise , Fluoretos/urina , Feminino , Prevalência , Adulto , Pessoa de Meia-Idade , Água Potável/análise , Água Potável/química , Osteocondroma/epidemiologia , Osteocondroma/induzido quimicamente , Adulto Jovem , Adolescente , Exposição Ambiental/análise , Fluorose Dentária/epidemiologia , Fluorose Dentária/etiologia , Criança , Idoso , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/induzido quimicamenteRESUMO
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/urinaRESUMO
BACKGROUND: Previous studies have shown a correlation between fluoride concentrations in urine and community water fluoride concentrations. However, there are no studies of the relationship between community water fluoridation, urine, serum, and amniotic fluid fluoride concentrations in pregnant women in the US. The aim of this study was to determine the relationship between maternal urine fluoride (MUF), maternal urine fluoride adjusted for specific gravity (MUFSG), maternal serum fluoride (MSF), amniotic fluid fluoride (AFF) concentrations during pregnancy, and community water fluoridation in Northern California. METHODS: Archived samples of urine, serum and amniotic fluid collected from second trimester pregnant women in Northern California from 47 different communities in Northern California and one from Montana (n = 48), were analyzed for fluoride using an ion specific electrode following acid microdiffusion. Women's addresses were matched to publicly reported water fluoride concentrations. We examined whether fluoride concentrations in biospecimens differed by fluoridation status of the community water, and determined the association between water fluoride concentrations and biospecimen fluoride concentrations using linear regression models adjusted for maternal age, smoking, Body Mass Index (BMI), race/ethnicity, and gestational age at sample collection. RESULTS: Fluoride concentrations in the community water supplies ranged from 0.02 to 1.00 mg/L. MUF, MSF , and AFF concentrations were significantly higher in pregnant women living in communities adhering to the U.S. recommended water fluoride concentration (0.7 mg/L), as compared with communities with less than 0.7 mg/L fluoride in drinking water. When adjusted for maternal age, smoking status, BMI, race/ethnicity, and gestational age at sample collection, a 0.1 mg/L increase in community water fluoride concentration was positively associated with higher concentrations of MUF (B = 0.052, 95% CI:0.019,0.085), MUFSG (B = 0.028, 95% CI: -0.006, 0.062), MSF (B = 0.001, 95% CI: 0.000, 0.003) and AFF (B = 0.001, 95% CI: 0.000, 0.002). CONCLUSIONS: We found universal exposure to fluoride in pregnant women and to the fetus via the amniotic fluid. Fluoride concentrations in urine, serum, and amniotic fluid from women were positively correlated to public records of community water fluoridation. Community water fluoridation remains a major source of fluoride exposure for pregnant women living in Northern California.
Assuntos
Líquido Amniótico/química , Fluoretação , Fluoretos/metabolismo , Exposição Materna/estatística & dados numéricos , Adulto , California , Água Potável/química , Feminino , Feto/química , Fluoretos/sangue , Fluoretos/urina , Humanos , Montana , Gravidez , Segundo Trimestre da Gravidez , Adulto JovemRESUMO
Rationale: Potential adverse effects of fluoride on neurodevelopment has been extensively explored and mitochondria have been recognized as critical targets. Mitochondrial biogenesis serves a crucial role in maintaining mitochondrial homeostasis and salubrious properties of resveratrol (RSV) has been well-defined. However, the molecular mechanisms governing mitochondrial biogenesis in developmental fluoride neurotoxicity remain unclear and the related therapeutic dietary agent is lacking. Methods: In vitro neuroblastoma SH-SY5Y cells and in vivo Sprague-Dawley rat model of developmental fluoride exposure were adopted. A total population of 60 children under long-term stable fluoride exposure were also recruited. This work used a combination of biochemical and behavioral techniques. Biochemical methods included analysis of mitochondrial function and mitochondrial biogenesis, as well as mRNA and protein expression of mitochondrial biogenesis signaling molecules, including silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Behavioral studies investigated spatial learning and memory ability of rats. Results: Both in vivo and in vitro experiments showed that sodium fluoride (NaF) caused mitochondrial dysfunction and impaired mitochondrial biogenesis. Also, NaF elevated SIRT1 levels and suppressed SIRT1 deacetylase activity along with decreased levels of PGC-1α, NRF1 and TFAM, suggestive of dysregulation of mitochondrial biogenesis signaling molecules. Moreover, enhancement of mitochondrial biogenesis by TFAM overexpression alleviated NaF-induced neuronal death through improving mitochondrial function in vitro. Further in vivo and in vitro studies identified RSV, the strongest specific SIRT1 activator, improved mitochondrial biogenesis and subsequent mitochondrial function to protect against developmental fluoride neurotoxicity via activating SIRT1-dependent PGC-1α/NRF1/TFAM signaling pathway. Noteworthy, epidemiological data indicated intimate correlations between disturbed circulating levels of mitochondrial biogenesis signaling molecules and fluoride-caused intellectual loss in children. Conclusions: Our data suggest the pivotal role of impaired mitochondrial biogenesis in developmental fluoride neurotoxicity and the underlying SIRT1 signaling dysfunction in such neurotoxic process, which emphasizes RSV as a potential therapeutic dietary agent for relieving developmental fluoride neurotoxicity.
Assuntos
Fluoretos/toxicidade , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Animais , Antioxidantes/farmacologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Criança , Modelos Animais de Doenças , Feminino , Fluoretos/urina , Humanos , Testes de Inteligência , Transtornos do Neurodesenvolvimento/induzido quimicamente , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/patologia , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuína 1/genéticaRESUMO
Chronic kidney disease of uncertain etiology (CKDu) is a common health issue among farming communities in the dry zone of Sri Lanka where groundwater fluoride is known to be higher than recommended levels. Excessive environmental ingestion of fluoride is widely considered as a possible factor for the onset of CKDu. This study was carried out to evaluate the serum and urine fluoride levels in biopsy-proven, non-dialysis CKDu patients. Control subjects were selected from the same area without any deteriorated kidney functions. Serum and urine fluoride levels were determined by ion-selective electrode method. Higher content of serum and urine fluoride levels were observed in patients with chronic renal failures. In CKDu cases, the serum fluoride concentrations ranged between 0.47 and 9.58 mg/L (mean 1.39 ± 1.1 mg/L), while urine levels were varied between 0.45 and 6.92 mg/L (mean 1.53 ± 0.8 mg/L). In patients, urine fluoride levels showed a significant difference with the CKDu stage; however, no difference was obtained between genders and age. In endemic controls, serum and urine fluoride levels ranged between 0.51 and 1.92 mg/L (mean = 1.07 ± 0.3 mg/L) and 0.36 and 3.80 mg/L (mean = 1.26 ± 0.6 mg/L), respectively. Significantly higher fluoride in serum and urine was noted in CKDu patients compared to endemic control groups. Higher fluoride exposure via drinking water is possibly the reason for higher fluoride in serum, while excessive urinary excretion would be due to deterioration of the kidney, suggesting a possible nephrotoxic role of environmental fluoride exposure.
Assuntos
Fluoretos/sangue , Fluoretos/urina , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Adulto , Idoso , Estudos de Casos e Controles , Água Potável , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Sri Lanka/epidemiologia , Adulto JovemRESUMO
A number of epidemiological studies have reported that chronic exposure to high concentrations of fluoride not only causes dental and skeletal fluorosis but additionally affects serum levels of reproductive hormones. However, possible interaction between fluoride exposure and estrogen receptor alpha (ESRα) gene polymorphisms on sex hormone-binding globulin (SHBG) and androgen binding protein (ABP) of male farmers has not been detailed. Here, we conducted a cross-sectional study including 348 male farmers with different fluoride exposure levels from drinking water in Henan province of China to explore effects of fluoride exposure and ESRα genetic variation on serum SHBG and ABP levels. We found serum SHBG levels in male farmers from the high exposure group to be lower than those of the low exposure group. We also found that concentrations of SHBG affected ABP levels. Furthermore, fluoride exposure and single nucleotide polymorphisms at the XbaI and rs3798577 loci of the ESRα gene affected serum ABP levels. Our findings suggest that chronic fluoride exposure from drinking water is associated with alterations of serum SHBG and ABP concentrations in local male farmers and that the effect of fluoride exposure on ABP levels vary depending on ESRα gene polymorphisms.
Assuntos
Proteína de Ligação a Androgênios/sangue , Água Potável/química , Receptor alfa de Estrogênio/genética , Fazendeiros , Fluoretos/toxicidade , Globulina de Ligação a Hormônio Sexual/metabolismo , China , Estudos Transversais , Exposição Ambiental/análise , Feminino , Fluoretos/metabolismo , Fluoretos/urina , Interação Gene-Ambiente , Genótipo , Hormônios , Humanos , Modelos Lineares , Masculino , Análise Multivariada , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Occupational exposure to the waste anaesthetic gases (WAGs) is a crucial problem for healthcare personnel. Cancer is among the potential long-term adverse effects of WAGs. The present occupational molecular epidemiology study was conducted in healthcare personnel (anaesthetists, nurses and technicians; n = 46), working in operating rooms (ORs; n = 34) and recovery units (RUs; n = 12) of the same hospital, to assess the genotoxicity risk of WAGs exposure. Twenty-one healthy available hospital staff allocated to other wards, without the history of working in ORs and RUs were the control group. A micronucleus test was carried out for peripheral blood lymphocytes (PBLs) and buccal epithelial cells (BECs). Exposure to the anaesthetics was assessed with sevoflurane concentrations and inorganic fluoride levels in post-shift urine samples of the healthcare staff. As an exposure marker, sevoflurane concentrations in ORs and RUs were measured using passive samplers. The micronuclei frequencies were increased in both PBLs (approximately two times) and BECs (approximately three times) of the healthcare personnel. Urinary sevoflurane concentrations exceeded the biological equivalent level in 23 personnel. Air sevoflurane levels in the breathing zone in three ORs and one RU did not exceed the established occupational exposure limits. Both in surrogate tissue (PBLs) and in target tissue (BECs) of the personnel of RUs and ORs of the same hospital, the genotoxicity risk was evident and similar. Originality of this study, in addition to the WAGs exposure confirmation of the healthcare personnel, was the involvement of the RU personnel for the genotoxicity assessment, which was the first time in the scientific literature.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Salas Cirúrgicas , Sala de Recuperação , Sevoflurano/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/análise , Anestésicos Inalatórios/análise , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Fluoretos/urina , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Testes para Micronúcleos , Mucosa Bucal/citologia , Exposição Ocupacional/análise , Recursos Humanos em Hospital , Sevoflurano/análise , Resíduos/efeitos adversos , Resíduos/análiseRESUMO
Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18-77â¯years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρâ¯=â¯0.7419, pâ¯<â¯0.0001), with median values of 1.5â¯mg/L and 2⯵g/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55â¯ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15â¯ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (ßâ¯=â¯0.56, pâ¯<â¯0.001), Cys-C (ßâ¯=â¯0.022, pâ¯=â¯0.001), KIM-1 (ßâ¯=â¯0.048, pâ¯=â¯0.008), OPN (ßâ¯=â¯0.38, pâ¯=â¯0.041), and eGFR (ßâ¯=â¯0.49, pâ¯=â¯0.03); however, CLU (ßâ¯=â¯0.07, pâ¯=â¯0.100) and TFF-3 (ßâ¯=â¯1.14, pâ¯=â¯0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.
Assuntos
Arsênio/efeitos adversos , Exposição Ambiental/efeitos adversos , Fluoretos/efeitos adversos , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Adolescente , Adulto , Idoso , Albuminúria/induzido quimicamente , Albuminúria/diagnóstico , Albuminúria/urina , Arsênio/urina , Biomarcadores/urina , Clusterina/urina , Estudos Transversais , Cistatina C/urina , Monitoramento Ambiental/métodos , Feminino , Fluoretos/urina , Taxa de Filtração Glomerular/efeitos dos fármacos , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Nefropatias/urina , Masculino , México , Pessoa de Meia-Idade , Osteopontina/urina , Valor Preditivo dos Testes , Medição de Risco , Fator Trefoil-3/urina , Poluentes Químicos da Água/urina , Adulto JovemRESUMO
The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis. The aim of this study was to evaluate the fluoride-associated nephrotoxicity. A total of 156 patients with childhood nephrotic syndrome were screened and it was observed that 32 of them had significantly high levels ( p ≤ 0.05) of fluoride in urine (4.01 ± 1.83 ppm) and serum (0.1 ± 0.013 ppm). On the basis of urinary fluoride concentration, patients were divided into two groups, namely group 1 (G-1) ( n = 32) containing normal urine fluoride (0.61 ± 0.17 ppm) and group 2 (G-2) ( n = 32) having high urine fluoride concentration (4.01 ± 1.83 ppm). Age-matched healthy subjects ( n = 33) having normal levels of urinary fluoride (0.56 ± 0.15 ppm) were included in the study as control (group 0 (G-0)). Kidney biopsies were taken from G-1 and G-2 only, who were subjected to ultrastructural (transmission electron microscopy) and apoptotic (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling) analysis. Various subcellular ultrastructural changes including nuclear disintegration, chromosome condensation, cytoplasmic ground substance lysis, and endoplasmic reticulum blebbing were observed. Increased levels of apoptosis were observed in high fluoride group (G-2) compared to normal fluoride group (G-1). Various degrees of fluoride-associated damages to the architecture of tubular epithelia, such as cell swelling and lysis, cytoplasmic vacuolation, nuclear condensation, apoptosis, and necrosis, were observed.
Assuntos
Apoptose/efeitos dos fármacos , Fluoretos/efeitos adversos , Túbulos Renais/efeitos dos fármacos , Síndrome Nefrótica/induzido quimicamente , Poluentes Químicos da Água/efeitos adversos , Biópsia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fluoretos/sangue , Fluoretos/urina , Humanos , Marcação In Situ das Extremidades Cortadas , Túbulos Renais/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Síndrome Nefrótica/sangue , Síndrome Nefrótica/patologia , Síndrome Nefrótica/urina , Projetos Piloto , Poluentes Químicos da Água/sangue , Poluentes Químicos da Água/urinaRESUMO
Objective: To investigate the epidemiological features of abnormal urinary fluoride rates in population with occupational exposure, and its relationships with age, work years and gender in Shanghai. Methods: A questionnaire survey was conducted respectively in 4 999 exposed workers and 283 non-exposed people during 2012-2015. Their urine samples were collected in plastic bottles and the fluoride ion selective electrode method was used for urinary fluoride level analysis. Logistic regression model was used to estimate associations between the abnormal rates and demographic/socioeconomic status of the study subjects. Results: In the past 4 years, the abnormal urinary fluoride rates (≥1.6 mg/L) in the population with occupational exposure was about 14.38%, it was about 1.43% in the control groups without occupational exposure. Their geometric mean of urinary fluoride content was 0.95 mg/L and 0.46 mg/L, respectively. The incidences of the abnormal rates in those aged ≥50 years and 34-39 years were 19.15% and 22.39%, respectively. The abnormal rate in males was 16.87%, much higher than that in females (6.85%). The abnormal rate had an upward trend along with the increased work years, especially in those with work years of ≥20 years. The abnormal rate was 23.28% in those with work years of ≥20 years and 13.29% in those with work years of <4 years. The relative risk for abnormal urinary fluoride rates was higher in male group, older age group and longer work year group, the odds ratio was 2.28, 1.10 and 1.13, respectively. Conclusions: Serious challenges exist in occupational health supervision. The relevant national standards should be updated as soon as possible. Males, those aged >50 years, and those with longer work years are the risk groups for intervention measures. More efforts are needed, such as strengthening the innovative application of health examination data and the equalization of basic public health service with comprehensive occupational health supervision programs among off-farm workers in the new medical reform.
Assuntos
Fluoretos/urina , Exposição Ocupacional/efeitos adversos , Fosfatos/urina , Adulto , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P < 0.001) higher levels of mean fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.
Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/urina , Morte Celular , Eritrócitos , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/urina , Talassemia/sangue , Talassemia/urina , Adolescente , Criança , Índices de Eritrócitos , Feminino , Fluoretos/administração & dosagem , Fluoretos/efeitos adversos , Fluoretos/sangue , Fluoretos/urina , Hematócrito , Hemoglobinas/análise , Humanos , Masculino , Tailândia , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was to explore the influence of fluoride exposure and ERα gene polymorphisms on reproductive hormone concentrations of women in accordance with endemic fluorosis residence. METHODS AND STUDY DESIGN: A cross sectional study was conducted in Tongxu county, Henan Province, China. A total of 679 women were recruited using cluster sampling and each subject provided fasting blood and an associated urine sample. We measured the concentrations of serum gonadotropin releasing hormone (GnRH), follicle-stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride. RESULTS: In the defluoridation project group (DFPG), serum GnRH was lower in women carrying C/C genotype compared to in those carrying C/T and T/T genotypes of ERα gene rs3798577 (p<0.05). In the endemic fluorosis group (EFG), serum GnRH was lower in women carrying Pp genotype compared to in those carrying PP and pp genotypes of ERα PvuII (p<0.05). Serum GnRH in women from EFG who carried Pp, pp, Xx and xx genotypes in ERα gene PvuII and XbaI was lower than in those in the control group (CG) who carried same genotypes (p<0.05). Furthermore, serum GnRH in women from EFG was significantly lower than in those in CG, regardless of whether the women were carrying C/C, C/T or T/T genotypes of ERα rs3798577 (p<0.05). Serum estradiol concentrations in EFG were significantly lower than in CG when the women were carrying the Pp, Xx and T/T genotypes in ERα gene (p<0.05). CONCLUSION: Interaction of ERα gene and fluoride exposure may influence women's serum reproductive hormone concentrations.
Assuntos
Doenças Endêmicas , Receptor alfa de Estrogênio/genética , Intoxicação por Flúor/epidemiologia , Intoxicação por Flúor/genética , Fluoretos/efeitos adversos , Hormônios/sangue , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Exposição Ambiental , Estradiol/sangue , Feminino , Fluoretos/urina , Fluorose Dentária , Hormônio Foliculoestimulante/sangue , Genótipo , Hormônio Liberador de Gonadotropina/sangue , Humanos , Hormônio Luteinizante , Pessoa de Meia-Idade , Polimorfismo Genético , Adulto JovemRESUMO
Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/µl) and miR-423 (189 copies/µL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents.
Assuntos
Arsênio/urina , Cromo/urina , Poluentes Ambientais/urina , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Arsênio/análise , Arsênio/sangue , Biomarcadores/urina , Criança , Pré-Escolar , Cromo/análise , Cromo/sangue , Creatinina/sangue , Água Potável/análise , Exposição Ambiental , Poluentes Ambientais/análise , Poluentes Ambientais/sangue , Feminino , Fluoretos/análise , Fluoretos/sangue , Fluoretos/urina , Taxa de Filtração Glomerular , Água Subterrânea/análise , Humanos , Nefropatias/sangue , Nefropatias/urina , Chumbo/análise , Chumbo/sangue , Chumbo/urina , Lipocalina-2/urina , Masculino , México , MicroRNAs/urina , Albumina Sérica/análiseRESUMO
The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women.