Wei Q, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L. A mini review of fluoride-induced apoptotic pathways. Environ Sci Pollut Res Int. 2018 Oct 18. doi: 10.1007/s11356-018-3406-z.
Fluorine or fluoride can have toxic effects on bone tissue and soft tissue at high concentrations. These negative effects include but not limited to cytotoxicity, immunotoxicity, blood toxicity, and oxidative damage. Apoptosis plays an important role in fluoride-induced toxicity of kidney, liver, spleen, thymus, bursa of Fabricius, cecal tonsil, and cultured cells. Here, apoptosis activated by high level of fluoride has been systematically reviewed, focusing on three pathways: mitochondrion-mediated, endoplasmic reticulum (ER) stress-mediated, and death receptor-mediated pathways. However, very limited reports are focused on the death receptor-mediated apoptosis pathways in the fluoride-induced apoptosis. Therefore, understanding and discovery of more pathways and molecular mechanisms of fluoride-induced apoptosis may contribute to designing measures for preventing fluoride toxicity.
Jiang P, Li G, Zhou X, Wang C, Qiao Y, Liao D, Shi D. Chronic fluoride exposure induces neuronal apoptosis and impairs neurogenesis and synaptic plasticity: Role of GSK-3β/β-catenin pathway. Chemosphere. 2018 Sep 17;214:430-435. doi: 10.1016/j.chemosphere.2018.09.095.
Fluoride is becoming an ineluctable environmental pollutant and its longterm exposure would cause fluorosis and irreversible brain damage, but the molecular mechanisms remain far from fully understood. In the present study, we firstly evaluated the glycogen synthase kinase 3β (GSK-3β)/β-catenin pathway in the hippocampus of rats exposed to fluoride, given the well-established role of GSK-3β/β-catenin pathway in neuronal death and survival. Our data showed that sustained exposure to 50 mg/L and 100 mg/L NaF in drinking water dose-dependently induced neuronal loss and apoptosis in rat hippocampus. Neurogenesis was also weakened by fluoride administration in the hippocampal dentate gyrus region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic density 95 (PSD95) protein levels, were decreased by 100 mg/L NaF treatment, whereas 50 mg/L NaF only reduced SYP expression, indicating a compromised synaptic function. We further demonstrated that NaF, especially the higher dose, induced GSK-3β activity, with decreased inactive phosphorylated GSK-3β levels and increased GSK-3β, the active form of the kinase. Correspondingly, downstream β-catenin signaling was undermined by NaF treatment as evidenced by the fact that both two doses of NaF decreased nucleus β-catenin status and the higher dose of NaF also reduced cytoplasmic β-catenin protein expression. Taken together, the present study firstly showed the aberrant changes of GSK-3β/β-catenin signaling in the fluoride-exposed brain, highlighting the involvement of GSK-3β/β-catenin signaling in the fluoride-induced neurotoxicity.
I’m somewhat surprised that this study has no control group or that the findings were not compared to a town of similar size with no fluoride. Comparing results to national statistics is not very informative. In a limited study such as this observing health effects other than dental fluorosis is unlikely.
Sezgin BI, Onur ŞG, Menteş A, Okutan AE, Haznedaroğlu E, Vieira AR. Two-fold excess of fluoride in the drinking water has no obvious health effects other than dental fluorosis. J Trace Elem Med Biol. 2018 Dec;50:216-222. doi: 10.1016/j.jtemb.2018.07.004. Epub 2018 Jul 11.
BACKGROUND: There is concern that fluorides in the drinking water is hazardous to health.
METHODS: We conducted an observational study in the village of Hanliyenice (population 280), Turkey, which has 2.5 times higher than optimal levels of fluoride in the drinking water and evaluated all children 7-13 years of age (N = 30). We collected information on dental decay, fluorosis, daily water consumption and diet, child history and her family history of cancer, cardiovascular risks/diseases, and asthma, and obtained a blood sample for extraction of genomic DNA. We genotyped ten single nucleotide polymorphisms in aquaporins.
RESULTS: As expected, a high number of children were dental caries free (19 out of 30) and had fluorosis (25 out of 30). Family history of cancer, cardiovascular events, and asthma was not different from the expected figures based on Turkey. One variant just upstream of AQP5 was associated with being fluorosis free. (G allele of AQP5 rs296763, p = 6.0E-6).
CONCLUSIONS: Exposure to levels of fluoride twice as high than the optimum in the drinking water increases the prevalence of fluorosis, dramatically decreases dental caries, and does not increase the risk of cancer, cardiovascular events, and asthma.
Santra D, Mandal S, Santra A, Ghorai UK. Cost effective and wireless portable device for estimation of hexavalent Chromium, Fluoride and Iron in drinking water. Anal Chem. 2018 Oct 3. doi: 10.1021/acs.analchem.8b03337.
The quality of drinking water often remains unknown to the people because of the inadequacy of cost-effective testing systems that can be used in field. Major portable instruments for water quality analysis include Ion Selective Electrodes (ISE) or Colorimeters. These are low cost devices but in case of multiple analyte detection like hexavalent Cr, Fluoride (F-) and Iron (Fe) with single instrumentation, no portable systems are available till date as per the authors’ knowledge. In this paper, we demonstrate the working of a low cost (approximate price INR 1500 or US $ 20) portable colorimetric system that can be operated with android smartphones wirelessly to estimate the contamination levels of Cr(VI), F-, or Fe in drinking water. This system also generates absorption spectra by recording absorbance of the analyte using Light Dependent Resistor (LDR) sensor. An android application software named “Spectruino” is developed to calculate the concentration of the analytes. We strongly believe that this cost-effective portable system will be very useful to ensure the drinking water quality throughout the continent to improve human health.
Harriehausen CX, Dosani FZ, Chiquet BT, Barratt MS, Quock RL. Fluoride Intake of Infants from Formula. J Clin Pediatr Dent. 2018 Oct 5. doi: 10.17796/1053-4625-43.1.7.
OBJECTIVE: This study aimed to assess fluoride intake in infants from formula reconstituted with water, with fluorosis risk in mind.
STUDY DESIGN: Data on water source, formula brand/type, volume of formula consumption and infant weight were collected for infants at two-, four-, six-, nine- and twelve-month pediatrician well child visits. Identified formula brands and water types were reconstituted and analyzed for fluoride concentration. Patient body mass and volume consumed/day were used to estimate fluoride intake from reconstituted formula. Descriptive statistics, one-way analysis of variance and chi-square tests were utilized.
RESULTS: All infants consumed formula reconstituted with minimally fluoridated water (0.0- 0.3 ppm). 4.4% of infants exceeded the recommended upper limit (UL) of 0.1mg/kg/day. Although mean daily fluoride consumption significantly differed among all groups, the proportion of infants at each visit milestone that exceeded daily fluoride intake of 0.1mg/kg/day was not statistically significantly different (p>0.05) for any age group. Predicted values calculated with optimally fluoridated water (0.7ppm) resulted in 36.8% of infants exceeding the UL.
CONCLUSIONS: Optimally fluoridated water may increase fluorosis risk for patients younger than six months. Future investigation should include multiple sites and multi-year follow-up to assess actual fluorosis incidence.
Zuo H, Chen L, Kong M, Qiu L, Lü P, Wu P, Chen K. Toxic effects of fluoride on organisms. Life sciences. 2018 Apr 1;198:18-24. doi: 10.1016/j.lfs.2018.02.001.
Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead to mitochondrial damage, endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity.
Perera T, Ranasinghe S, Alles N, Waduge R. Effect of fluoride on major organs with the different time of exposure in rats. Environmental health and preventive medicine. 2018 May 16;23(1):17. doi: 10.1186/s12199-018-0707-2.
BACKGROUND: High fluoride levels in drinking water in relation to the prevalence of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka were investigated using rats as an experimental model.
METHOD: The effects of fluoride after oral administration of Sodium fluoride (NaF) at levels of 0, 0.5, 5 and 20 ppm F– were evaluated in adult male Wistar rats. Thirty-six rats were randomly divided into 4 groups (n = 9), namely, control, test I, II, and III. Control group was given daily 1 ml/rat of distilled water and test groups I, II, and III were treated 1 ml/rat of NaF doses of 0.5, 5, and 20 ppm, respectively, by using a stomach tube. Three rats from the control group and each experimental group were sacrificed after 15, 30, and 60 days following treatment. Serological and histopathological investigations were carried out using blood, kidney, and liver.
RESULTS: No significant differences were observed in body weight gain and relative organ weights of the liver and kidney in fluoride-treated groups compared to control group. After 60 days of fluoride administration, group I showed a mild portal inflammation with lytic necrosis while multiple areas of focal necrosis and various degrees of portal inflammation were observed in groups II and III. This was further confirmed by increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. As compared with control and other treated groups, group III showed a significantly higher serum AST activity (p < 0.05) and ALT activity (p < 0.05) after 60 days and ALP activity with a significant difference (p < 0.05) after 15, 30, and 60 days. The renal histological analysis showed normal histological features in all groups with the elevated serum creatinine levels in group III compared to those in the groups I and II (p < 0.05) after 60 days. Significantly elevated serum fluoride levels were observed in group II of 30 and 60 days and group III after 15, 30, and 60 days with respective to control groups (p < 0.05).
CONCLUSION: Taken together, these findings indicate that there can be some alterations in liver enzyme activities at early stages of fluoride intoxication followed by renal damage.