ArticlePDF AvailableLiterature Review

Abstract

The behavior of fluoride ions in the human organism is a classic example of double-edged sword. On the one hand the daily supplementation with fluoride is undoubtedly an important preventing factor in protecting teeth from caries, and, as an important mitogenic stimulus for osteoblasts, it may enhance mineral deposition in bone, but on the other hand fluoride, above a threshold concentration, has been demonstrated to be toxic. We present here a brief review of fluoride metabolism and exposure, its use in caries prevention and its effects on bone, followed by an updating about the main hypotheses concerning its mechanism of action and toxicity. The effects of fluoride have been related mainly to its ability to evoke the activation of G proteins and the inhibition of phosphotyrosine phosphatases, leading to an intracellular increase of tyrosine phosphorylation and activation of the mitogen-activated protein kinase pathway, and its capacity to cause generation of reactive oxygen species. We present also a unifying hypothesis accounting for these apparently different effects, although the available experimental models and conditions are highly variable in the literature. A lot of experiments still need to be performed to clarify the positive and negative effects of fluoride. Finding the mechanisms accounting for fluoride toxicity is an important point: indeed, the use of fluoride has been proposed in the preparation of new biomaterials to be inserted in the bone, in order to improve their stable and safe integration.
A preview of the PDF is not available
... Although they contain high concentration, the utilization is poor due to the short retention time and low retention amounts. Such delivery subject to limited control may also lead to the overuse of fluorides, which can cause dental fluorosis and affect the balance of the oral microbiome 20 . Thus, a controlled topical drug delivery solution is in urgent need of oral applications. ...
Article
Full-text available
Dental caries caused by oral microbiome dysbiosis with the elevation of acidogenic bacteria is the most prevalent non-communicable disease worldwide. Early prevention and timely fluoride treatment are crucial for caries lesion management. Herein, to address the challenges of in situ sensing and topical drug delivery within the oral cavity, a miniaturized, battery-free, and wearable dental patch system was developed for microenvironment monitoring and controlled fluoride treatment. With the integration of near-field communication, the dental patch realizes wireless energy harvesting and data transmission with mobile terminals like smartphones when attached conformally to the tooth surface. The acidic microenvironment caused by bacterial metabolism are electrochemically detected, while fluorides can be delivered locally from the electric-responsive drug delivery electrode for on-demand treatment. As flexible electronics armed to the teeth, this intraoral theranostic wearable system provides an inspiring platform for point-of-care monitoring and treatment of dental caries and oral diseases.
... Fluoride is considered a micronutrient that naturally presents in plants, animal residues, soil, and water (Naderi et al. 2020). However, fluoride in drinking water functions as a two-sided sword which means it is both beneficial in lower concentrations and toxic at higher concentrations if consumed for a long time (Gazzano et al., 2010). Where in some parts of the world facing a fluoride deficiency, several countries are also severely affected by its toxicity (Kashyap et al. 2021). ...
Article
Safe drinking water is a key ingredient to a sustainable life for mankind. Fluoride is considered a micronutrient required in a minute quantity for the proper functioning of bones and teeth in humans. However, its higher concentration could lead to toxic effects on skeletal and dental health. The amount of fluoride required can be easily achieved through the consumption of vegetables, cereals, and drinking water (within desirable limits). Fluoride beyond the limits in groundwater has become a major issue in most of the states of India while Rajasthan has been considered as most severely affected with fluorosis where all the districts were reported with a high concentration of fluoride in groundwater. Adsorption technique was recently developed as a low-cost method that can potentially remove excess fluoride from groundwater. Numerous adsorbent developed so far has been discussed in this review to explore their potential for defluoridation. The ability of this method greatly depends on the development of adsorptive materials. It was found after the literature survey that several types of adsorbent using chemicals as well as vegetative waste have been developed and studied to quantify the removal capacity of fluoride from water. However, their utility on the water is still needed to be studied to explore these adsorbents for commercial use leading to the improvement in water quality.
... The results showed a decrease in serum calcium levels only in the fluoride group compared to the rest of the groups, and this corresponds to many studies that attributed to the fact that fluoride interferes with the metabolism of calcium (30,31). ...
... Water fluoridation includes the process of controlling the fluoride concentration in order to stay within the permissible limit. Fluoride in water is often referred to as a double-edged sword (Gazzano et al. 2010;Goldberg 2018;Adeyeye, 2021). This essentially means that at concentrations lower than 0.5 mg/L, drinking water consumers are receptive to dental carries and cavities, while on the other hand, a higher concentration than 1.5 mg/L can cause dental fluorosis, skeletal fluorosis, and other negative effects which will be later discussed in the section. ...
Article
Full-text available
Groundwater is a key resource in the world. Its importance is often undermined, despite the various applications which include irrigation, drinking, sanitation, and industrial uses. One of the contaminants of groundwater is fluoride or the fluorine ion. Fluoride is a common pollutant of water, carrying potential benefits and costs to various sectors. Fluoride contamination of groundwater can impact humans, animals, healthcare, and the agricultural sector in direct or indirect ways. This paper aims to establish the definition of fluoride contamination of groundwater and simultaneously provide an outline of a few common sources that may cause fluoride contamination. Furthermore, this study will lay out the impacts of fluoride-contaminated groundwater on two sectors: healthcare and agriculture/irrigation. This study will also summarize various other research projects conducted across the world, which deliver promising evidence to support the points made throughout the paper. In addition to a detailed analysis of the impacts of fluoride on the healthcare and agricultural sector, this study also evaluates few other challenges which this issue poses and how to overcome them in the near future. A summation of deflouridation techniques is included, along with the future scope pertaining to the field of fluoride contamination. Another objective of the study is to spread awareness about the various health impacts that fluoride contamination poses and encourages consumption of fluoride in accordance with the set limit of 0.5–1.5 mg/L. The motivation behind writing this review is to compile and document various researches, along with an address on this prevalent issue to minimize the detrimental impacts and potential health risks on the society. The results of this study help to minimize risks in the future and encourage scientists to come up with mitigation strategies to ensure a safer environment.
... However, Nawlakhe and Bulusu (1989) have reported that skeletal and crippling fluorosis may occur when drinking water has high F i.e. more than 3 mg/l and consumed for 8-10 years. The severity of fluorosis depends on the level of fluoride content and duration of its exposure (Gazzano et al., 2010). Thus, excess intake of fluoride cause dental, skeletal and crippling fluorosis and non-skeletal fluorosis (Zhang et al., 2003). ...
Article
Full-text available
In India more than 70% population relay on ground water for their daily needs. Ground water may be contaminated from natural contaminants e.g. fluoride, iron, arsenic and salinity etc. It has been proved that more than 21 states of Indian Republic are suffering from fluoride problem in their ground water. It is pertinent to mention here that fluoride in water and diet has both i.e. positive as well as negative effects on animals including humans. Haryana is one of the states facing the problem of fluorosis hence; the study under reference was carried out to monitor the level of fluoride in groundwater of Bapoli block of Panipat district of Haryana. In Bapoli block fluoride content varied between 0.24 - 1.76 mg/l and mean fluoride content was 0.99 mg/l. Out of 40 samples analyzed from Bapoli block, 34 samples had fluoride content within permissible limit and 06 samples had fluoride content above the permissible limit. The different studies carried out globally have shown that underground water includes larger amount of fluoride. It may be due to dissolution of fluoride minerals from rocks laden with fluoride minerals.
Article
The aim of this research was to obtain hydroxyapatite (HAp)-based coatings doped with different concentrations of Mg on a Ti nanostructured surface through electrochemical techniques and to evaluate the influence of Mg content on the properties of HAp. The undoped and doped HAp-based coatings were electrochemically deposited in galvanostatic pulsed mode on titania nanotubes with a diameter of ~72 nm, being designed to enhance the adhesion of the HAp coatings to the Ti substrate. The obtained materials were investigated by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction (XRD), and Fourier-Transform Infra-Red spectroscopy (FTIR). The adhesion of the coatings to the substrate was also evaluated with the help of the “tape-test” and the micro-scratch test. The morphology (SEM) of all the coatings is made of very thin and narrow ribbon-like crystals, with some alterations with respect to the Mg amount in the coatings. Thus, a concentration of 1 mM of Mg in the electrolyte leads to wider and thicker ribbon-like crystals, while a concentration of 1.5 mM in the electrolyte generated a morphology that resembles the undoped HAp. Both phase composition (XRD) and chemical bonds (FTIR) analysis proved the formation of HAp in all coatings. Moreover, according to XRD, all coatings have a strong orientation toward the (002) plane. Irrespective of the Mg content, all coatings registered an average roughness between approx. 500 and 600 nm, while the coating thickness increased after addition of Mg, from a value of 9.6 μm, for the undoped HAp, to 11.3 μm and ~13.7 μm for H/Mg1 and H/Mg2, respectively. In terms of adhesion, it was shown that the coatings a H/Mg2 had a poorer adhesion when compared to H/Mg1 and the undoped HAp (H), which registered similar adhesion, indicating that a concentration of 1.5 mM of Mg in the electrolyte reduces the adhesion of the Hap-based coatings to the nanostructured surface. The obtained results indicated that Mg concentrations up to 1 mM in the electrolyte can enhance the properties of HAp-based coatings electrochemically deposited on a nanostructured surface, while even a slightly higher concentration of 1.5 mM can negatively impact the characteristics of HAp coatings.
Article
Coumarin based Sensor 1 has been designed and synthesized to recognize fluoride ion visually with high selectivity and sensitivity over other anionic analytes through color change from very faint yellow to pink in acetonitrile. The probable binding phenomenon in solution phase has been explained by 1H NMR study of sensor 1 with different concentration of fluoride ions. The binding constant of the sensor 1 with fluoride has been determined as 3.9 × 104 M−1 and the lower detection limit 6.5 µM of the sensor 1 towards fluoride, which has made the sensor 1 as a promising backbone for selective detection of fluoride. For the practical application, test strips based on sensor 1 were fabricated, which could act as a convenient and efficient naked eye F− test kits. The experimentally observed absorption maxima along with its binding nature with fluoride ions also have been supported through theoretical calculations using density functional theory (DFT) calculations.
Article
Full-text available
Fluoride, as the smallest anion except hydride (H–), has garnered considerable attention over the past decades due to its specific physiochemical properties and its crucial roles in many biological, chemical, medical and environmental processes. There have been hitherto a number of reviews published, to our knowledge, most of which focus on instrumental analytical methods, nanomaterial probes, bio–material sensors, and organic small molecular chemosensors for F⁻ detection. Macrocycles including cages have blossomed over the past half century and found most appealing to the discovery of efficient, sensitive and selective approaches for fluoride detection. This review summarizes recent advances in the development of macrocyclic receptors, including calix[4]pyrrole–based receptors, calixarene–based receptors, pillararene–based receptors, and cage–based receptors, for selective recognition of fluoride since 2013. Particularly, the focus of this review will be on design principles, structural features, working mechanism (complexation or deprotonation), and recognition efficacy and selectivity of macrocyclic receptors, as well as their recognition–based applications in fluoride sensing, extraction, transmembrane fluoride transport, nanodevice and logic gate construction. It is expected that this review article could provide a guide for rational design and synthesis of, inter alia, new macrocyclic receptors for selective fluoride recognition, thereby advancing fluoride recognition–based applications in new and practical directions.
Article
Magnetic resonance imaging (MRI) is a molecular imaging technology that has been widely adopted in biomedical and clinical diagnostics fields owing to its capability of deep tissue imaging with high spatiotemporal resolution. Responsive small molecule MRI contrast agents, known as MRI probes, are of particular interest for the detection and visualisation of target analytes in vitro and in vivo, thus expanding MRI’s capability into the molecular imaging regime. Each of the responsive MRI probe selectively responds to corresponding target analyte and then gives the magnetic resonance (MR) signal change for this analyte detection. In this work, advances in developing responsive MRI probes based on gadolinium(III) (Gd(III)) complexes are systematically summarized. Specifically, we first introduce the strategies in developing Gd(III) complex probes through different response mechanisms, and then discuss the progresses in developing Gd(III) complex-based resposnvie MRI probes for different target analytes, including biologically relevant cations, anions, pH, biomolecules and redox homeostasis. Responsive bimodal probes, such as MRI-fluorescence probes, MRI-PET probes, and MRI-SPECT probes are then briefly outlined. The applications of Gd(III) complex-based responsive probes in in vivo and in vitro MRI are also included. Current limitations and future research directions in developing Gd(III) complex probes for MR analysis and imaging are also proposed. It is anticipated that this work will promote the ongoing research on developing Gd(III) complex-based MRI probes and their applications in understanding the bioactive analytes’ pathophysiological processes.
Article
Fluoride has gained widespread attention as a target for binding by synthetic receptors during the past decades, because of its key roles in the environmental and biological processes. This review aims to provide a broad assessment of the reported examples of coordinated fluoride/hydrated-fluoride complexes of neutral receptors offered by natural hydrogen-bond donating sites from hydroxyl, amine, amide, thioamide, urea, and thiourea functionalities. The review primarily focuses on the structural aspects of fluoride binding by both acyclic (monopodal, dipodal, tripodal, hexapodal) and cyclic neutral receptors, as gathered from 2010 onwards. Examples relating to selective solid-state capture of fluoride in its bare or hydrated forms by these polytopic acycles or cyclic receptors are the primary focus of this review. Additionally, a brief discussion on fluoride selective sensing by less preorganized monopodal sensors in solution state is included.
Article
Full-text available
Fluoride-modification of dental titanium (Ti) implants is used to improve peri-implant bone growth and bone-to-implant contact and adhesion strength. In this study, the surface topography, chemistry and biocompatibility of polished Ti surfaces treated with hydrofluoric acid solution (HF) were studied. Murine osteoblasts (MC3T3-E1) were cultured on the different groups of Ti surfaces. Surfaces treated with HF had higher roughness, lower cytotoxicity level and better biocompatibility than controls. For short treatment times (40 and 90 s), fluorine was detected only within the first 5 nm of the surface layer (X-ray Photoemission Spectroscopy, XPS), whereas longer treatment time (120 and 150 s) caused fluoride ions to penetrate deeper (Secondary Ion Mass Spectrometry, SIMS). These results suggest that submerging Ti implants in a weak HF solution instigate time-dependant specific surface changes that are linked to the improved biocompatibility of these surfaces.
Article
Full-text available
Bioactive glasses such as Hench's 45S5 (Bioglass) have applications to tissue engineering as well as bone repair, and the insertion of fluoride in their composition has been proposed to enhance their bioactivity. In view of a potential clinical application, we investigated whether fluoride-containing glasses exert toxic effects on human MG-63 osteoblasts, and whether and how fluoride, which is released in the cell culture medium, might play a role in such cytotoxicity. A 24h incubation with 50 microg/ml (12.5 microg/cm(2)) of fluoride-containing bioactive glasses termed HCaCaF(2) (F content: 5, 10 and 15 mol.%) caused the release of lactate dehydrogenase in the extracellular medium (index of cytotoxicity), the accumulation of intracellular malonyldialdehyde (index of lipoperoxidation), and the increase of glutathione consumption. Furthermore, fluoride-containing glasses inhibited the pentose phosphate oxidative pathway and the glucose 6-phosphate dehydrogenase activity. These effects are ascribable to the fluoride content/release of glass powders, since they were mimicked by NaF solutions and were prevented by dimethyl sulfoxide and tempol (two radical scavengers), by superoxide dismutase (a superoxide scavenger), and by glutathione (the most important intracellular antioxidant molecule), but not by apocynin (an inhibitor of NADPH oxidase). The presence of fluoride-containing glasses and NaF caused also the generation of reactive oxygen species, which was prevented by superoxide dismutase and catalase. The data suggest that fluoride released from glasses is the cause of MG-63 cell oxidative damage and is independent of NADPH oxidase activation. Our data provide a new mechanism to explain F(-) ions toxicity: fluoride could trigger, at least in part, an oxidative stress via inhibition of the pentose phosphate oxidative pathway and, in particular, through the oxidative inhibition of glucose 6-phosphate dehydrogenase.
Article
Abnormal level of fluoride in phreatic groundwater causes serious health hazards in humans and physiological damages in plants. This study showed that occurrence of fluoride is highly sporadic and localized in eastern and southeastern Karnataka and the concentration of fluoride varies from 1 to 7.4 mg/l. The geological strata near the wells influence the fluoride content in phreatic groundwater. Effective and cheap methods of defluoridation are few and hence biological defluoridation may be the best alternative to the conventional methods.
Article
Fluoride is an important element for mineralization of body tissues. The use of topical and systemic fluoride for oral health has resulted in major reductions in dental caries and its associated disability. Fluoridation of public water supplies has been endorsed by over 90 professional health organizations as the most effective dental public health measure in existence. Still, about half of the US population fails to receive the maximum benefits possible from community water fluoridation and the use of fluoride products. Fluoride also plays a role in bone health. The role of high doses of fluoride for prevention of osteoporosis is undergoing active study and is considered experimental at this point. Dietetics professionals should routinely monitor and promote the use of systemic and topical fluorides, especially in children and adolescents. The American Dietetic Association strongly reaffirms its endorsement of the use of systemic and topical fluorides, including water fluoridation, at appropriate levels of intake, as an important public health measure. However, clients should be cautioned that, experimental use of high intakes of fluoride should be avoided unless they are participating in clinical trials.
Article
Serotonin (5-hydroxytryptamine; 5-HT) caused a transient increase in intracellular Ca2+ in C6BU-1 glioma cells in a concentration-dependent manner; half maximally at 73 nM. The 5-HT2 agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane also increased the levels of intracellular Ca2+ whereas the 5-HTιc agonist l-(3-chlorophenyl)piperazine and 5-HT1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin were completely ineffective. Ketanserin and spiperone blocked the response to 5-HT at a nanomolar concentration, but the 5-HT3 antagonist MDL 72222 had no effect on it. Thus 5-HT2 receptors are responsible for activating Ca2+ mobilization in C6 glioma cells. Treatment of C6 glioma cells with dexamethasone potentiated the ability of 5-HT to cause intracellular Ca2+ mobilization in both a dose- and time-dependent manner. The dose-response curve for 5-HTwas shifted 9-fold to the left compared to controls, and the Vmax value was also significantly enhanced. This enhanced Ca2+ mobilization was completely inhibited by ketanserin dose-dependently. In addition, the treatment with dexamethasone enhanced fluoride-activated Ca2+ mobilization, suggesting that the enhanced GTP binding protein function is one of the mechanisms responsible for the enhancement of the 5-HT response induced by dexamethasone treatment. This enhancement of agonist activity was mediated by the type II glucocorticoid receptor (GR) since RU 38486, an inhibitor of the type II GR, antagonized the dexamethasone-induced enhancement.Copyright © 1992 S. Karger AG, Basel
Article
The aim of the present study was to investigate the biological mechanisms of the functional attachment of fluoride-modified titanium implants to cortical bone by studying the association of the pull-out test results with gene expression of osteoblast (runx2, osteocalcin, collagen-I and IGF-I), osteoclast (TRAP, H+-ATPase and calcitonin receptor) and inflammation (TNF-α, IL-6 and IL-10) markers from peri-implant bone tissue using real-time RT–PCR, following a 4- and 8-week healing period. After implant detachment, wound fluid from the implant site was collected for LDH and ALP activity analysis. A new method to study volumetric bone mineral density (vBMD) of sub-implant cortical bone was developed using micro-computed tomography. Our results show lower LDH activity and TRAP mRNA levels in fluoride implants after 4 weeks of healing, yet no differences were found either on the pull-out force or expression of bone formation marker genes. After 8 weeks of healing, both pull-out, vBMD and osteocalcin, runx2 and collage type I gene expression were higher in fluoride implants. In conclusion, fluoride-modified implants seem to modulate both inflammation and bone resorption/formation events at the bone–implant interface, suggesting that these biological effects are an intrinsic part of the clinical performance of this surface.
Article
Sodium fluoride at a dose level of 5.0 mg/kg enhanced aminopyrine N-demethylase and NADPH cytochrome c reductase activities and cytochrome P450 and cytochrome b5 levels in rat liver, kidney, lung, intestine and testis, whereas acetanilide hydroxylase activity remained unchanged in kidney and lung and was increased in liver, intestine and testis. Sodium fluoride at 20.0 mg/kg caused a decrease in aminopyrine N-demethylase, acetanilide hydroxylase and NADPH cytochrome c reductase activities and cytochrome P450 and cytochrome b5 levels in all tissues, except for an increase in NADPH cytochrome c reductase activity in the intestine and testis. Fluoride at both dose levels produced only marginal changes in glutathione-S-transferase activity except for a 4-fold increase in the testis at 5.0 mg/kg. Sodium fluoride at 5.0 mg/kg increased lipid peroxidation in all tissues studied. At 20.0 mg/kg there was a decrease in lipid peroxidation in liver, lung and testis and an increase in kidney and intestine.