The effect of fluoride intake on the total lipid,cholesterol and vitamin E levels in a sera and liver of guinea pigs on high fat diet

Guinea pigs were raised on a diet containing 18 percent fat and were provided 25 or 0 ppm fluoride in the drinking water. Animals were sacrificed at the end of 0, 3, 6, 9 and 13 weeks on the dietary regimen and blood serum was analyzed for fluoride, total lipid, cholesterol and alpha tocopherol. The serum total lipid levels, cholesterol and alpha tocopherol levels were increased in the high fluoride group between 9 and 13 weeks. An increase in total lipid and alpha tocopherol levels was also observed in the livers of these animals. The increase in liver content of alpha tocopherol was proportional to the increase in total lipid content whereas the corresponding increase in serum alpha tocopherol content was significant even when the increase in total lipid was taken into account. The data suggest a specific effect of fluoride on the serum alpha tocopherol levels of the high fluoride animals.     

Health risk assessment of fluoride in water distribution network of Mashhad,Iran

High and low levels of fluoride in drinking waters have been considered as a major public health issue in recent years. This cross-sectional study was conducted over five consecutive years (from 2012 to 2016) in the water distribution network of Mashhad city, Iran with the objectives of determining levels of fluoride and to perform health risk assessment among residents in the study area. Water samples were taken from 30 stations and were analyzed using UV-visible spectrophotometer. The mean annual concentrations of fluoride in all stations during five years of consecutive study were lower than the respective maximum permissible limits (1.5 mg/L) in water as regulated by the WHO. The human health risk assessment was performed by calculating the chronic daily intake and hazard quotient (HQ) of fluoride through human oral intake for adults (men and women) and children for each year during a five-year study. Health risk analysis in this study presented that the non-carcinogenic risk associated with fluoride exposure through drinking water in Mashhad was mostly acceptable because the mean HQ values of fluoride were lower than 1.     

High Concentration of Fluoride Can Be Increased Risk of Abortion

The presence of fluoride in drinking water can be either beneficial or harmful for human health, depending on its concentration. Most adverse effects of fluoride are observed at high concentrations (above 1.5 mg/L). This study was aimed to evaluate the effect of fluoride concentrations in drinking water on spontaneous abortion in two regions: one with low fluoride concentration and another with high fluoride concentration. The results showed that there is a relationship between the concentration of fluoride in drinking water and abortion, so that the risk of abortion increased at high concentrations of fluoride. However, further studies are needed to clarify this relationship due to the small area and population in this study.     

Variations in concentration of fluoride in blood plasma of pregnant women and their possible consequences for amelogenesis in a fetus

The aim of the study was to assess the fluoride exposure of pregnant women living in Poznan (Poland) by examination of fluoride levels in blood plasma.

The subjects of the study were 31 pregnant women aged 22–34 years in the course of regular pregnancy. Data concerning the sources of fluoride exposure such as diet, oral hygiene measures and topical application of fluoride procedures, were collected from each individual with a questionnaire. Samples of blood plasma were drawn in the 28th, 33rd week of pregnancy and during delivery. The analysis evaluating the fluoride concentration in the samples was carried out with the use of fluoride electrode ORION (model 96-09). The data were statistically analyzed using the program Statistica for Windows.

Mean value of fluoride concentration in the samples of blood plasma from the 28th week of pregnancy was lower than the mean concentration detected in the 33rd week of pregnancy (3.29 and 3.73 μmol/l, respectively). These values suggest that apart from drinking water, there were other important sources of fluoride in the examined sample.

The results indicate that a reliable assessment of fluoride exposure in a given population cannot be based solely on the concentration of fluoride in drinking water. Relatively high levels of fluoride in blood plasma of examined women suggest that there is no need for fluoride supplementation in this group of patients.     

Association of Hypertension,Body Mass Index,and Waist Circumference with Fluoride Intake; Water Drinking in Residents of Fluoride Endemic Areas,Iran

Hypertension is becoming a global epidemic for both rural and urban populations; it is a major public health challenge in Iran. Fluoride can be a risk factor for hypertension. Cross-sectional analysis was conducted in two study areas to assess the relation of fluoride with blood pressure prevalence, BMI, waist circumference, and waist-to-hip ratio (WHR) among different age groups in both sexes. The mean value of fluoride concentration in the drinking water from the four study villages varied from 0.68 to 10.30 mg/L. The overall prevalence of HTN and prehypertension in all subjects was 40.7%. The prevalence of isolated systolic hypertension, isolated diastolic hypertension, systolic-diastolic hypertension, and prehypertension in the total sample population was 1.15, 0.28, 9.53, and 29.76%, respectively. The odd ratio of hypertension in residents who drank water with high fluoride levels was higher than that in residents who drank water with lower level of fluoride (OR 2.3, 1.03–5.14). Logistic regression results showed that age (P?<?0.001), sex (P?=?0.018), BMI (P?=?0.015), and the fluoride level in drinking water (P?=?0.041) had a significant relationship with increased blood pressure. There were no statistically significant correlations between fluoride and BMI, hip circumference, and waist to hip ratio (WHR). The findings of this study are important for health care personnel and policymakers.     

Fluoride and environmental health: a review

The relationship between environmental fluoride and human health has been studied for over 100 years by researchers from a wide variety of disciplines. Most scientists believe that small amounts of fluoride in the diet can help prevent dental caries and strengthen bones, but there are a number of adverse affects that chronic ingestion at high doses can have on human health, including dental fluorosis, skeletal fluorosis, increased rates of bone fractures, decreased birth rates, increased rates of urolithiasis (kidney stones), impaired thyroid function, and lower intelligence in children. Chronic occupational exposure to fluoride dust and gas is associated with higher rates of bladder cancer and variety of respiratory ailments. Acute fluoride toxicity and even death from the ingestion of sodium fluoride pesticides and dental products have also been reported. The distribution of fluoride in the natural environment is very uneven, largely a result of the geochemical behavior of this element. Fluorine is preferentially enriched in highly evolved magmas and hydrothermal solutions, which explains why high concentrations are often found in syenites, granitoid plutonic rocks, alkaline volcanic, and hydrothermal deposits. Fluoride can also occur in sedimentary formations that contain fluoride-bearing minerals derived from the parent rock, fluoride-rich clays, or fluorapatite. Dissolved fluoride levels are usually controlled by the solubility of fluorite (CaF₂); thus, high concentrations are often associated with soft, alkaline, and calcium-deficient waters. Although much is known about the occurrence and health effects of fluoride, problems persist in Third World countries, where populations have little choice in the source of their drinking water and food. However, even in developed nations, fluoride ingestion can exceed the recommended dose when sources other than drinking water are ignored.     

Assessing groundwater quality and health risks of fluoride pollution in the Shasler Vagu (SV) watershed of Nalgonda,India

Abstract

The principal objectives of this study were to evaluate groundwater quality and human health risks of fluoride contamination in Shasler Vagu (SV) watershed of Nalgonda district, India. For this purpose, 107 groundwater samples were collected and analyzed various physcio-chemical parameters including fluoride, and Gibbs diagrams, Hill–Piper trilinear diagram, and groundwater quality index (GWQI) were applied to understand the groundwater chemistry and its suitability for drinking purpose. In addition to this, non-carcinogenic health risks of high fluoride intake were also evaluated using the US Environmental Protection Agency model for adults and children in the study region. Groundwater chemistry is mainly controlled by HCO₃^?-Ca²⁺-Mg²⁺ and Na⁺-HCO₃^? type, and rock weathering. Assessment of GWQI indicates that 76% of groundwater sources in the study region have poor quality for drinking uses. Results reveal that fluoride concentration ranged from 1.4 to 5.9?mg/L in the groundwater samples, which was significantly higher than the recommended limit of 1.5?mg/L for drinking uses. Results of hazard quotient (HQ) estimates are in the ranges of 0.90–3.78 and 1.21–5.11 in adults and children populations of the study region, respectively. About 98% of adults and 100% of children population of SV watershed are at very high risks of chronic toxicity by excess fluoride intake.     

Health-risk assessment related to the fluoride,nitrate, and nitrite in the drinking water in the Sanandaj,Kurdistan County,Iran

The concentration of fluoride and nitrate in groundwater is usually higher than that of surface water. The main objective of this study was to estimate the health-risk assessment associated with fluoride, nitrate, and nitrite in drinking water in Sanandaj and its villages. The number of samples in the Sanandaj and its rural was 106. The average concentration of fluoride in urban and rural drinking water was 0.22 mg/l and 0.27 mg/l, respectively. Fluoride concentration was also close to urban and rural drinking water. The concentration of nitrate in urban and rural drinking water was in the range between 0.28–27.77 mg/l and 1.28–80 mg/l, respectively. The concentration of nitrate reported in rural samples was higher than that of urban samples. The maximum concentration of nitrate reported in this study was 80 mg/l. The mean CDI for nitrate in the men, women, and children was 0.4258, 0.5110, and 1.1454, respectively. The findings of this study indicated that all three groups studied were exposed to nitrate contact hazards (HQ > 1). Therefore, the HQ in each of the three groups was higher than 1, which should be carefully monitored and necessary measures should be performed.     

Effect of drinking waters of high fluorine content on the urinary fluoride level.

The urinary fluoride level has been studied in 307 subjects consuming drinking waters of different fluoride concentrations. The urinary fluoride level was found to increase with the fluoride content of the drinking water. The urinary F level of the population group drinking water of optimum fluoride concentration was 1.14 mg of fluoride per litre. Thus, in regions where the drinking water contains an insufficient amount of fluoride, the fluoride content of domestic salt must be adjusted so as to ensure an about 1.14 mg/litre urinary F level of the population.     

Pre and Post Natal Exposure of Fluoride Induced Oxidative Macromolecular Alterations in Developing Central Nervous System of Rat and Amelioration by Antioxidants

The effect of fluoride exposure during gestation and post gestation periods were studied to check the status of oxidant, antioxidant and macromolecular changes in CNS and ameliorative role of antioxidants. The pregnant Wistar albino rats were exposed to 50 and 150 ppm fluoride in drinking water and the pups born to them were used for experimentation. After postpartum, the pups were administered daily selected antioxidants through oral gavage. On 21st postnatal day pups were sacrificed and biochemical parameters were assessed. Fluoride exposure substantially increased the activity/levels of fluoride, LPO, protein oxidation, MAO-B, GOT, GPT and decreased protein thiols, RNA and total proteins in discrete regions of CNS. The findings evidenced fluoride induced dyshomeostasis caused on antioxidants, enzymes, macromolecules and governed the pathophysiological events leading to functional loss in a dose dependent manner. The administration of antioxidants remedied the disquiet caused by high fluoride exposure at extreme vulnerable periods of life.     

Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation

The mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress.     

Fluoride-induced lesions in the teeth of the short-tailed field vole (Microtus agrestis): A description of the dental pathology

The effect of fluoride on the appearance of the teeth of the short-tailed field vole. Microtus agrestis, was investigated in both wild animals collected from field sites affected by different levels of industrial fluoride contamination and laboratory-reared animals consuming experimental grass diets of known fluoride concentration or with known fluoride concentrations in drinking water. The extent and severity of lesions on the surface and structure of both incisors and molars are described as six lesion types and related to the amount of biologically available orally ingested fluoride. In the incisors of voles consuming relatively low fluoride diets, lesions are mainly confined to those resulting from disruption of enamel pigmentation expressing itself as concentric bands of pigmentation-free areas on incisor surfaces. The visible effects on molars at low fluoride levels are confined to minor alterations in surface appearance. At higher levels of available dietary fluoride, effects on enamel pigmentation are superseded by alterations in the formation, composition, and strength of both enamel and dentine. The incisors exhibit a marked to severe increase in the cutting tip erosion rates with comparable increases in the extent of abnormal surface changes (enamel hypoplasia) and loss of enamel pigmentation. The grinding surfaces of molars from animals exposed to high levels of dietary fluoride exhibit increasingly severe erosion of outer enamel regions, combined with cavitation and staining of the exposed central dentine. The mechanisms through which fluoride elicits increasingly visible and pathological alterations to the surface and subsurfaces of rodent teeth are discussed. J Morphol 232: 155–167, 1997. © 1997 Wiley-Liss, Inc.     

Effects of Fluoride on Expression of P450, CREM and ACT Proteins in Rat Testes

Fluoride (F) is an essential trace element that humans and animals ingest from water, air, and fluoride-containing products; however, excessive fluoride absorption can damage a variety of organs and tissues, including the male reproductive system. Our previous studies found that fluoride exposure lowered sperm quality and interfered with spermatogenesis; however, the exact mechanism remained unclear. Proteins cytochrome P450 (P450), cAMP-responsive element modulator (CREM), and activator of CREM in testis (ACT) play the key roles in spermatogenesis and sperm motility. To investigate whether fluoride affects the expression of P450, CREM, and ACT, we used immunohistochemical techniques to determine expression levels of these proteins in testes of rats administered 100 mg NaF/L for 2 weeks via drinking water. The results showed that P450 expression was decreased while CREM and ACT expression was increased in the fluoride group, compared to the control. These data suggest that fluoride can impair male reproduction by affecting expression of P450, CREM, and ACT in the testes.     

Reversal of fluoride induced cell injury through elimination of fluoride and consumption of diet rich in essential nutrients and antioxidants

The objective of the present communication is to address the issues concerning reversal of fluoride induced cell injury and disease (i.e. fluorosis) through the elimination of fluoride and consumption of a diet containing essential nutrients and antioxidants. Humans afflicted with fluorosis, as a result of consuming fluoride contaminated water or food, have been investigated. Hospital based diagnostic procedure for early detection of fluorosis, through retrieval of history, clinical complaints, testing of blood, urine and drinking water for fluoride using ion selective electrode technology, along with X-ray of the forearm have been carried out. Confirmed cases of fluorosis were introduced to an intervention protocol consisting of (1) provision of safe drinking water with fluoride levels less than 1 mg/L and (2) counselling on nutritional supplementation with focus on adequate intake of calcium, vitamins C, E and antioxidants. The patients were monitored at frequent intervals up to one year and the results are reported. With a standardized early diagnosis, elimination of fluoride intake and supplementation of a diet rich in essential nutrients and antioxidants, we have shown that the fluorosis can be reversed.     

Reversal of fluoride induced cell injury through elimination of fluoride and consumption of diet rich in essential nutrients and antioxidants

The objective of the present communication is to address the issues concerning reversal of fluoride induced cell injury and disease (i.e. fluorosis) through the elimination of fluoride and consumption of a diet containing essential nutrients and antioxidants. Humans afflicted with fluorosis, as a result of consuming fluoride contaminated water or food, have been investigated. Hospital based diagnostic procedure for early detection of fluorosis, through retrieval of history, clinical complaints, testing of blood, urine and drinking water for fluoride using ion selective electrode technology, along with X-ray of the forearm have been carried out. Confirmed cases of fluorosis were introduced to an intervention protocol consisting of (1) provision of safe drinking water with fluoride levels less than 1 mg/L and (2) counselling on nutritional supplementation with focus on adequate intake of calcium, vitamins C, E and antioxidants. The patients were monitored at frequent intervals up to one year and the results are reported. With a standardized early diagnosis, elimination of fluoride intake and supplementation of a diet rich in essential nutrients and antioxidants, we have shown that the fluorosis can be reversed.     

Evaluation of the Content of Antimony,Arsenic, Bismuth,Selenium, Tellurium and Their Inorganic Forms in Commercially Baby Foods

The purpose of the investigation is to reveal the influence of dietary calcium on fluorosis-induced brain cell apoptosis in rat offspring, as well as the underlying molecular mechanism. Sprague–Dawley (SD) female rats were randomly divided into five groups: control group, fluoride group, low calcium, low calcium fluoride group, and high calcium fluoride group. SD male rats were used for breeding only. After 3 months, male and female rats were mated in a 1:1 ratio. Subsequently, 18-day-old gestation rats and 14- and 28-day-old rats were used as experimental subjects. We determined the blood/urine fluoride, the blood/urine calcium, the apoptosis in the hippocampus, and the expression levels of apoptosis-related genes, namely Bcl-2, caspase 12, and JNK. Blood or blood/urine fluoride levels and apoptotic cells were found significantly increased in fluorosis rat offspring as compared to controls. Furthermore, the Bcl-2 messenger RNA (mRNA) expression levels significantly decreased, and caspase 12 mRNA levels significantly increased in each age group as compared to controls. Compared with the fluoride group, the blood/urine fluoride content and apoptotic cells evidently decreased in the high calcium fluoride group, Bcl-2 mRNA expression significantly increased and caspase 12 mRNA expression significantly decreased in each age group. All results showed no gender difference. Based on these results, the molecular mechanisms of fluorosis-induced brain cell apoptosis in rat offspring may include the decrease in Bcl-2 mRNA expression level and increase in caspase 12 mRNA expression signaling pathways. High calcium intake could reverse these gene expression trends. By contrast, low calcium intake intensified the toxic effects of fluoride on brain cells.     

Lack of cytogenetic effects in mice or mutations in Salmonella receiving sodium fluoride.

We have examined the possible effect of fluoride intake on chromosome damage. There was no evidence of increased frequency of chromosomal aberration in bone marrow or testis cells of mice with either 50 ppm fluoride intake over several generations or 100 ppm intake for 6 weeks compared to animals drinking distilled water. Fluoride was not found to be mutagenic in a widely used bacterial mutagenesis assay over a range of 0.1 to as high as 2000 microgram fluoride per plate.     

Effect of maternal fluoride exposure on developing CNS of rats: protective role of Aloe vera, Curcuma longa and Ocimum sanctum

Fluoride is toxic to neuronal development and its excessive intake during pregnancy cause adverse effects on neonatal development. The present study examined the presence of oxidative stress during maternal exposure of fluoride and the therapeutic strategy of Aloe vera, Curcuma longa and Ocimum sanctum extracts in functional prevention of fluoride led oxidative stress. The pregnant Wistar rats were exposed to 100 ppm fluoride in drinking water and pups born to them were supplemented with phytoextracts daily. On 21st postpartum day, the pups were sacrificed to analyse fluoride and oxidative stress markers. Fluoride exposure significantly increased its accumulation, lipid peroxidation and decreased the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glutathione levels in discrete regions of the central nervous system (CNS) of pups indicating oxidative stress and inhibited antioxidant defense. The results implied the vulnerability of developing CNS to fluoride toxicity. On phytoextract supplementation, the oxidant devastation was suppressed by regaining antioxidant homeostasis near normal level proving efficacy and therapeutic strategy. Among the phytoextracts supplemented the Ocimum sanctum is found to be more effective.     

Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice

Arsenic and fluoride are potent toxicants, widely distributed through drinking water and food and often result in adverse health effects. The present study examined the effects of sodium meta-arsenite (100 mg/l in drinking water) and sodium fluoride (5 mg/kg, oral, once daily), administered either alone or in combination for 8 weeks, on various biochemical variables indicative of tissue oxidative stress and cell injury in Swiss albino male mice. A separate group was first exposed to arsenic for 4 weeks followed by 4 weeks of fluoride exposure. Exposure to arsenic or fluoride led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by increased level of blood and tissues reactive oxygen species (ROS) level. An increase in the level of liver and kidney thiobarbituric acid reactive substance (TBARS) along with a concomitant decrease in the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and reduced GSH content were observed in both arsenic and fluoride administered mice. The changes were significantly more pronounced in arsenic exposed animals than in fluoride. It was interesting to observe that during combined exposure the toxic effects were less pronounced compared to the effects of arsenic or fluoride alone. In some cases antagonistic effects were noted following co-exposure to arsenic and fluoride. Arsenic and fluoride concentration increased significantly on exposure. Interestingly, their concentration decreased significantly on concomitant exposure for 8 weeks. However, the group which was administered arsenic for 4 weeks followed by 4 weeks of fluoride administration showed no such protection suggesting that the antagonistic effect of fluoride on arsenic or vice versa is possible only during interaction at the gastro intestinal sites. These results are new and interesting and require further exploration.     

Fluoride and diethylnitrosamine coexposure enhances oxido‐inflammatory responses and caspase‐3 activation in liver and kidney of adult rats

The present study investigated the impact of coexposure to fluoride and diethylnitrosamine (DEN) on hepatorenal function in adult rats. The animals were exposed to fluoride (15 mg/L in drinking water) and DEN (10 mg/kg) singly or coexposed to both compounds for 14 days. Results demonstrated that the fluoride or DEN mediated increase in hepatorenal toxicity was intensified in the coexposure group. Additionally, the decrease in antioxidant enzyme activities as well as the elevation in reactive oxygen and nitrogen species, and lipid peroxidation was markedly aggravated in rats coexposed to DEN and fluoride. Furthermore, the increase in levels of nitric oxide, tumor necrosis factor‐α and interleukin‐1β, myeloperoxidase and caspase‐3 activities as well as histological lesions was more pronounced in the liver and kidney of rats coexposed to DEN and fluoride. Conclusively, coexposure to fluoride and DEN exacerbated hepatorenal damage via enhancement of oxido‐inflammatory responses and caspase‐3 activation in rats.