Search Results (19)

Chronic inflammation is a hallmark of brain tumors, especially gliomas, which exhibit elevated levels of pro-inflammatory mediators within the tumor and its microenvironment. Metabolic disturbances triggered by fluoride as a pro-oxidative agent in glioma cells, known for their high aggressiveness and resistance to therapy—remain poorly understood. Therefore, investigating the impact of physiologically elevated fluoride concentrations on oxidative stress and pro-inflammatory responses in glioma cells represents a relevant and timely research objective. Methods: U-87 human glioblastoma cells were subjected to short-term and long-term exposure to physiologically high concentrations of NaF (0.1–10 µM). Both the cells and the culture medium were analyzed. We assessed levels of reactive oxygen species (ROS), antioxidant defenses, and a panel of cytokines and chemokines. Results: Our results demonstrated that oxidative stress and inflammatory conditions in U-87 cells varied with fluoride concentration and exposure time. This led to an increase in ROS levels and key pro-inflammatory cytokines, including IL-6 and TNF-α. Conclusions: Fluoride compounds can generate ROS and disrupt the antioxidant defense system in U-87 human glioblastoma cells, leading to the initiation and progression of inflammatory states. Furthermore, prolonged exposure to NaF may induce adaptive mechanisms in U-87 cells. Full article

Fluoride-enriched geothermal groundwater poses chronic health risks (e.g., dental and skeletal fluorosis) through prolonged exposure; nevertheless, hydrochemical-driven factors and the genetic mechanism of fluoride enrichment in such systems remain inadequately identified. This study employed hydrochemical characterization, isotopic tracing, and health risk models to elucidate the genetic mechanism of fluoride-enriched geothermal groundwater. The key findings reveal the following. (1) Geothermal groundwater (Cl-Na type; TDS 90–345 mg/L; pH 6.25–7.42) contrasts with alkaline river water (pH 7.48–8.05; SO₄-Na/HCO₃-Na) and saline seawater (TDS 23.9–28.2 g/L). Stable isotopes (δD, δ¹⁸O) confirm atmospheric precipitation recharge with an elevation of 69–635 m. (2) The Self-Organizing Map algorithm categorized 30 geothermal samples into three groups: Cluster I—low temperature and pH, high TDS; Cluster II—high temperature, low F⁻ concentration; and Cluster III—low TDS, and high pH and F⁻ concentration. (3) Fluoride enrichment in Cluster III originated from the evaporite/fluorite dissolution under alkaline conditions and cation exchange interactions, while the inhibition of CaF₂ dissolution by reverse cation exchange limited the accumulation of F⁻ in Cluster II and Cluster III samples. (4) Health risks disproportionately affect children (80% high risk) and women, necessitating pre-use defluorination. Full article

Groundwater fluoride levels have begun to be a global concern, posing significant challenges to the safe utilization of water resources and mitigating potential impacts on human health. Chronic exposure to elevated levels of naturally occurring fluoride in groundwater affects millions worldwide. Prolonged exposure can lead to health issues such as dental fluorosis and skeletal fluorosis. The World Health Organization (WHO) has established a maximum fluoride concentration guideline of 1.5 mg/L for drinking water. However, groundwater quality is not regularly tested in many regions, leaving communities unaware if water sources, such as wells and springs, contain harmful fluoride levels. In the Balasore area, Odisha, India, rising fluoride concentrations and spatial variability necessitate accurate predictions for effective groundwater management. This article proposes four predictive models, Random Forest (RF), Support Vector Regression (SVR), Gradient Boosting (XGBoost), and Stacking Regressor (SR), to estimate fluoride concentrations using physicochemical parameters and sampling depth as predictor variables. The performance of these models is assessed using the coefficient of determination (accuracy), mean square error (MSE), and mean absolute error (MAE). This article compared fluoride concentrations of machine learning models, including SR, RF, XGBoost, and SVR, in groundwater in Balasore, Odisha. Based on predictive performance, an SR model yielded the lowest MSE and MAE scores at 0.01817 and 0.10327, respectively. These findings underscore the superiority of ensemble learning approaches in addressing complex datasets and provide a robust framework for effective groundwater fluoride management. This article highlights the potential of advanced machine learning in improving public health outcomes in fluoride-affected regions. Finally, the recommendations for decreasing the fluoride concentrations and the guidelines for future research will be proposed. Full article

Fluoride contamination in water sources presents critical public health challenges, particularly in regions where groundwater exhibits elevated fluoride levels. Chronic exposure can result in dental and skeletal fluorosis, necessitating efficient and sustainable remediation strategies. This study investigates the spherical agglomeration technique (SAT) as an alternative fluoride removal method, assessing the performance of sunflower oil versus n-heptane as humectants and evaluating the synergistic effects of Agave durangensis leaf extract. A factorial experimental design optimized dosage parameters in aqueous models and well water samples, ensuring reliable fluoride removal. Sunflower oil significantly outperformed n-heptane, achieving fluoride removal efficiencies of up to 95.19% under optimal conditions (5 mL _Hum/g _TMCs at pH 6.5). Incorporating A. durangensis extract sustained high fluoride removal while reducing the required extract dosage to 0.5 g _Extr/g _TMCs. When applied to well water samples, the SAT consistently maintained an 88.9% fluoride removal efficiency. Compared to conventional methods such as coagulation–flocculation and adsorption, the SAT demonstrated enhanced effectiveness with a lower environmental footprint. These findings reinforce the viability of sunflower oil and A. durangensis extract as eco-friendly alternatives to n-heptane, positioning the SAT as a scalable, cost-effective solution for large-scale fluoride remediation. Full article

Acute and short-term toxicity tests are foundational to toxicology research. These tests offer preliminary insights into the fundamental toxicity characteristics of the chemicals under evaluation and provide essential data for chronic toxicity assessments. Fluoride is a common chemical in aquatic environments; however, the findings of toxicological data, such as LC₅₀ for aquatic organisms, often exhibit inconsistency. Consequently, this study employed zebrafish as a model organism during their early life stages to assess the acute and short-term toxicity of fluoride exposure. Bayesian model averaging was utilized to calculate the LC₅₀/EC₅₀ values and establish baseline concentrations. The results indicated a dose–response relationship between water fluoride concentration and harmful outcomes. The 20 mg/L group was identified as the lowest observed adverse effect level (LOAEL) for the majority of toxicity indicators and warrants special attention. Based on the BBMD model averages, the LC₅₀ of fluoride for 1 to 5 days post-fertilization (dpf) zebrafish was 147.00, 80.80, 61.25, 56.50, and 37.50 mg/L, while the EC₅₀ of cumulative malformation rate for 5 dpf zebrafish was 59.75 mg/L. As the benchmark response (BMR) increased, both the benchmark concentrations (BMCs) and benchmark dose levels (BMDLs) also increased. The research aims to provide essential data for the development of environmental water guidelines and to mitigate ecological risks associated with fluoride in aquatic ecosystems. Full article

The exposure of humans to fluorine is connected with its presence in the air, food and water. It is well known that fluorides even at a low concentration but with long time exposure accumulate in the body and lead to numerous metabolic disorders. Fluoride is recognised as a factor modulating the energy metabolism of cells. This interaction is of particular importance in muscle cells, which are cells with high metabolic activity related to the metabolism of glucose and glycogen. In someone suffering from chronic fluoride poisoning, frequent symptoms are chronic fatigue not relieved by extra sleep or rest, muscular weakness, muscle spasms, involuntary twitching. The aim of this study was to examine the effect of fluorine at concentrations determined in blood of people environmentally exposed to fluorides on activity and expression of enzymes taking part in metabolism of muscle glycogen. CCL136 cells were cultured under standard conditions with the addition of NaF. The amount of ATP produced by the cells was determined using the HPLC method, the amount and expression of genes responsible for glycogen metabolism using WB and RT PCR methods and the amount of glycogen in cells using the fluorimetric and PAS methods. It has been shown that in CCL136 cells exposed to 1, 3 and 10 μM NaF there is a change in the energy state and expression pattern of enzymes involved in the synthesis and breakdown of glycogen. It was observed that NaF caused a decrease in ATP content in CCL136 cells. Fluoride exposure also increased glycogen deposition. These changes were accompanied by a decrease in gene expression and the level of enzymatic proteins related to glycogen metabolism: glycogen synthase, glycogen synthase kinase and glycogen phosphorylase. The results obtained shed new light on the molecular mechanisms by which fluoride acts as an environmental toxin. Full article

Chronic exposure to high levels of fluoride may cause health concerns, including in cognitive function. This study reviewed the evidence on the association between fluoride exposure and cognitive outcomes in children from gestation up to 18 years old. A literature search was conducted for studies on pregnant women and children below 18, exposed to any source of fluoride, and assessed with a validated cognitive tool. The data were analyzed using a systematic narrative synthesis approach and by subgroup: study design, age of participants, levels of fluoride exposure and methodological quality. Our search retrieved 15,072 articles, of which 46 met the inclusion criteria. Only 6 of the studies had a longitudinal design; the remainder were cross-sectional. The levels of fluoride exposure were ≥2 mg/L in 27 studies and <2 mg/L in 13 studies; 6 studies did not report levels of fluoride exposure. Only 1 of 5 studies graded as excellent quality showed a negative association between fluoride exposure and cognitive outcomes, whereas 30 of 34 poor and fair quality studies reported a negative association. The overall evidence from this review suggests that high fluoride exposure might be associated with negative cognitive outcomes in children. However, more longitudinal studies with high methodological quality are needed on this topic. Full article

Despite a strong body of evidence attesting to the effectiveness of fluoride (F) in preventing and controlling caries, some studies have sought to investigate the influence of F exposure on the salivary glands, organs that are essential for the maintenance of cavity homeostasis through salivary production, finding that exposure to F can cause biochemical and proteomic changes. Thus, this study aimed to investigate the morphological effects of prolonged exposure to F on the salivary glands of mice, at concentrations that would correspond to optimally fluoridated water (suitable for human consumption) and to fluorosis-endemic regions. Twenty-four male mice (Mus musculus) were divided into three groups, according to F levels in the drinking water: 0 (control), 10, or 50 mg F/L, with an exposure period of 60 days. The glands were morphometrically analyzed for the total acinar area, parenchyma area, and stromal area, as well as for the immunohistochemical analysis of myoepithelial cells. The results showed that prolonged exposure to F at 10 mg F/L did not promote significant changes in the morphometry of the salivary glands of mice, which reinforces the safety of the chronic use of F in low doses. Full article

Fluorides are compounds that can be found in the minerals of soil with volcanic rocks. Different populations are exposed to high levels of fluorides through drinking water that, due to their chronic intake, cause several types of damage to health. Nails and hair, denominated as recent biomarkers, have been employed for monitoring systemic fluoride from long-term exposure to fluorides. The aim of this study was to perform a systematic review of the use of recent biomarkers for monitoring systemic fluoride levels in exposed populations and verify their validity in the measurement of the fluorine (F⁻) concentration within the body. A digital search was performed in the databases PubMed/Medline, Springer Link, Cochrane, and Scopus of original articles that employed recent biomarkers for monitoring systemic F⁻. Seventeen articles were included in this analysis; the recorded variables were the F⁻ amount in each assessed biomarker, source of exposure, and total daily fluoride intake (TDFI). TDFI was associated with F⁻ in nails and hair, as well as the exposure through drinking water. In conclusion, recent biomarkers are adequate for monitoring the systemic fluoride levels by evaluating the chronic/subchronic exposure through different sources, mainly drinking water, considering nails better than hair for this purpose. Full article

Fluoride (F) exposure decreases brain receptor activity and neurotransmitter production. A recent study has shown that chronic fluoride exposure during childhood can affect cognitive function and decrease intelligence quotient, but the mechanism of this phenomenon is still incomplete. Extracellular matrix (ECM) and its enzymes are one of the key players of neuroplasticity which is essential for cognitive function development. Changes in the structure and the functioning of synapses are caused, among others, by ECM enzymes. These enzymes, especially matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are involved in both physiological processes, such as learning or memory, and pathological processes like glia scare formation, brain tissue regeneration, brain-blood barrier damage and inflammation. Therefore, in this study, we examined the changes in gene and protein expression of MMP2, MMP9, TIMP2 and TIMP3 in the prefrontal cortex, hippocampus, striatum and cerebellum of rats (Wistar) exposed to relatively low F doses (50 mg/L in drinking water) during the pre- and neonatal period. We found that exposure to F during pre- and postnatal period causes a change in the mRNA and protein level of MMP2, MMP9, TIMP2 and TIMP3 in the prefrontal cortex, striatum, hippocampus and cerebellum. These changes may be associated with many disorders that are observed during F intoxication. MMPs/TIMPs imbalance may contribute to cognitive impairments. Moreover, our results suggest that a chronic inflammatory process and blood-brain barrier (BBB) damage occur in rats’ brains exposed to F. Full article

The potential antioxidant property of Moringa oleifera (MO) has been the recent focus of an increased number of studies. However few studies investigated its antioxidative ability against sodium fluoride-induced redox balance breakdown in Oreochromis niloticus. Thus, this study evaluates the effects of MO against the oxidative stress induced by sub-chronic exposure to sodium fluoride (NaF). A total of 264 fish (40 ± 3 g BW) were used to calculate the 96 hr-LC50 of NaF and perform the sub-chronic exposure study. 96 hr-LC50 of NaF was calculated as (61 mg/L). The 1/10 dose of the calculated 96 hr-LC50 (6.1 mg/L) was used to complete the sub chronic exposure for eight weeks. Fish were divided into four groups (n = 51; three replicates each); control, non-treated group; NaF group (exposed to NaF 6.1 mg/L); MO group (treated with 1% MO of diet); and NaF+MO (exposed to NaF 6.1 mg/L and treated with 1% MO of diet). The results revealed that the sub-chronic exposure to NaF (6.1 mg/L) was substantially increased malondialdehyde (MDA) and decrease the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) in the gills, liver, kidney, and muscle tissue in a time-dependent manner. In addition, a significant reduction in mRNA expression of GST in the liver was reported following NaF exposure. On the contrary, dietary supplementation of MO to NaF-exposed fish resulted in a significant reduction in MDA levels, and a significant elevation of SOD, CAT, GSH, GPx, and TAC activities in a time-dependent manner, in addition to significant elevation of GST mRNA expression in liver tissue. It could be concluded that a 1% MO (w/w) ration is a promising antioxidant plant that may successfully use to interfere with the oxidation processes induced by NaF in various tissues of Oreochromis niloticus. Full article

Exposure of neural cells to harmful and toxic factors promotes oxidative stress, resulting in disorders of metabolism, cell differentiation, and maturation. The study examined the brains of rats pre- and postnatally exposed to sodium fluoride (NaF 50 mg/L) and activity of NADPH oxidase 4 (NOX4), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), concentration of glutathione (GSH), and total antioxidant capacity (TAC) in the cerebellum, prefrontal cortex, hippocampus, and striatum were measured. Additionally, NOX4 expression was determined by qRT–PCR. Rats exposed to fluorides (F-) showed an increase in NOX4 activity in the cerebellum and hippocampus, a decrease in its activity in the prefrontal cortex and hippocampus, and upregulation of NOX4 expression in hippocampus and its downregulation in other brain structures. Analysis also showed significant changes in the activity of all antioxidant enzymes and a decrease in TAC in brain structures. NOX4 induction and decreased antioxidant activity in central nervous system (CNS) cells may be central mechanisms of fluoride neurotoxicity. NOX4 contributes to blood–brain barrier damage, microglial activation, and neuronal loss, leading to impairment of brain function. Fluoride-induced oxidative stress involves increased reactive oxygen speciaes (ROS) production, which in turn increases the expression of genes encoding pro-inflammatory cytokines. Full article

A new form of chronic tubulointerstitial kidney disease (CKD) not related to diabetes or hypertension appeared during the past four decades in several peri-equatorial and predominantly agricultural countries. Commonalities include underground stagnation of drinking water with prolonged contact with rocks, harsh climatic conditions with protracted dry seasons, and rampant poverty and malnutrition. In general, the cause is unknown, and the disease is therefore named CKD of unknown aetiology (CKDu). Since it is likely caused by a combination of factors, a better term would be CKD of multifactorial origin (CKDmfo). Middle-aged malnourished men with more than 10 years of exposure to environmental hazards are the most vulnerable. Over 30 factors have been proposed as causative, including agrochemicals and heavy metals, but none has been properly tested nor proven as causative, and unlikely to be the cause of CKDmfo/CKDu. Conditions such as, having favourable climatic patterns, adequate hydration, and less poverty and malnutrition seem to prevent the disease. With the right in vivo conditions, chemical species such as calcium, phosphate, oxalate, and fluoride form intra-renal nanomineral particles initiating the CKDmfo. This article examines the key potential chemical components causing CKDmfo together with the risk factors and vulnerabilities predisposing individuals to this disease. Research findings suggest that in addition to drinking water from stagnant sources that contain high ionic components, more than 10 years of exposure to environmental nephrotoxins and micronutrient malnutrition are needed to contract this fatal disease. Full article

Excessive intake of fluoride can cause adverse health effects. Consumption of tea as a popular drink could be a potential source of fluoride exposure to humans. This research aimed to evaluate the fluoride concentration in tea among the Iranian people using the available data in the literature and to assess the health risk related to the consumption of tea in men, women, and children. The health risk assessment was conducted using the chronic daily intake and hazard quotient according to the approach suggested by the Environmental Protection Agency. The fluoride content in published studies varied noticeably, ranging from 0.13 to 3.27 mg/L. The results revealed that the hazard quotient (HQ) in age groups of women (21–72 years) and children (0–11 years) was within the safe zone (HQ < 1) which showed that there was no potential of non-carcinogenic risk associated with drinking tea in these groups. However, in one case of the men (21–72 years), the HQ > 1 which shows a probable risk of fluorosis. The order of non-carcinogenic health risks in the studied groups was in the order of men > women > children. The results of this can be useful for organizations with the responsibility of human health promotion. Full article

The continuous rise of autism spectrum disorder (ASD) prevalent in the past few decades is causing an increase in public health and socioeconomic concern. A consensus suggests the involvement of both genetic and environmental factors in the ASD etiopathogenesis. Fluoride (F) is rarely recognized among the environmental risk factors of ASD, since the neurotoxic effects of F are not generally accepted. Our review aims to provide evidence of F neurotoxicity. We assess the risk of chronic F exposure in the ASD etiopathology and investigate the role of metabolic and mitochondrial dysfunction, oxidative stress and inflammation, immunoexcitotoxicity, and decreased melatonin levels. These symptoms have been observed both after chronic F exposure as well as in ASD. Moreover, we show that F in synergistic interactions with aluminum’s free metal cation (Al³⁺) can reinforce the pathological symptoms of ASD. This reinforcement takes place at concentrations several times lower than when acting alone. A high ASD prevalence has been reported from countries with water fluoridation as well as from endemic fluorosis areas. We suggest focusing the ASD prevention on the reduction of the F and Al³⁺ burdens from daily life. Full article