Chronic Fluoride Research Articles

A Brief Review of Endemic Fluorosis in Dromedary Camels (Camelus Dromedarius) and Focus on Their FluorideSusceptibility

Chronic fluoride poisoning in the form of fluorosis in diverse species of domestic animals, viz. cattle (Bos taurus), water buffaloes (Bubalus bubalis), sheep (Ovis aries), goats (Capra hircus), horses (Equus caballus), donkeys (Equus asinus), and dromedary camels (Camelus dromedarius) is the resultant of prolonged consumption or exposure of high fluoride through drinking water, food, and air. In general, fluorosis can be recognised by the presence of dental mottling (dental fluorosis) and bone deformities (skeletal fluorosis). In animals, skeletal fluorosis often results in reduced mobility as a result of bone damages or changes due to exostosis, osteosclerosis, osteoporosis, and osteophytosis. In addition, fluoride-induced non-skeletal disorders like gastro-intestinal disturbances, neurological disorders, reproductive dysfunctions, apoptosis, excitotoxicity, genotoxicosis, and teratogenic effects have also been observed in fluorosed domestic and experimental animals. The maximum prevalence, 19.4% and 17.9% of dental and skeletal fluorosis at >3.0 ppm fluoride concentration in drinking water has been observed in domesticated dromedary camels in India, respectively. The prevalence and severity of fluorosis varies from one fluoride endemic region to another and depends on a number of determinants or factors. However, the major determinants are fluoride concentration and its frequency and duration of exposure, rate and density of bio-accumulation of fluoride, and food nutrients. Among different species of domestic animals, camels are found to be less susceptible to fluoride or have a relatively higher fluoride tolerance. In present communication, fluorosis in camels, determinants of fluoride toxicity, and fluoride susceptibility in camels are briefly and critically reviewed. Simultaneously, research gapes have also been highlighted for further research work on chronic fluoride intoxication in diverse species of animals. This review is significant for researchers in understanding of chronic fluoride toxicity in grazers (cattle and buffalo) and browsers (equines, flocks, and camels).

Epidemiological, Biological, Physical and Radiological Surveys for the Diagnosis of Adult Skeletal Fluorosis in the Rift Valley Region of Ethiopia: A Single Point Prevalence Study

Fluoride is often referred to as a double-edged sword, as insufficient intake is associated with dental caries; excessive intake leads to dental and skeletal fluorosis. The toxic effects of fluoride can be classified as acute and chronic. The acute toxicity of fluoride occurs after a single ingestion of a large amount of fluoride. On the other hand, the chronic toxicity of fluoride is caused by long-term ingestion of the chemical element. Skeletal fluorosis is the result of chronic fluoride toxicity. Fluorosis is an endemic disease in several geographic areas of several countries, including the Rift Valley region of Ethiopia. Nevertheless, there are few epidemiological data on skeletal fluorosis. This study was initiated to determine the prevalence of skeletal fluorosis among adults in the Rift Valley region of Ethiopia. A single-point cross-sectional prevalence study was conducted between January 2023 and February 2023 to determine the prevalence of skeletal fluorosis in adults who met the inclusion criteria. Radiologic, biological (serum and urinalysis), and physical examinations were performed to collect the required data. Physical examinations included assessments of Range of Motion (RMO), muscle strength, and dermatomes of the upper and lower extremities' major joints, muscles, and nerve roots. In addition, the stress tests developed by Susheela and Bhatnagar [1] were used as part of the physical examination to diagnose the disease. After analyzing the musculoskeletal, radiological and biological data of the 42 study participants, the prevalence of skeletal fluorosis was calculated to be 21.4% (n=9). This prevalence rate indicates the importance of immediate intervention, including defluoridation and public education.

A Review on Experimentally Proven Medicinal Plants and Their Constituents against Fluoride Toxicity.

Fluoride toxicity, principally by polluted groundwater, is regarded as a momentous global public health risk, as there is no particular and proven treatment for chronic fluoride toxicity i.e., fluorosis which leads to several serious health complications. Scientific literature reveals several medicinal plants and natural products alleviate experimentally induced fluoride toxicity. The present review attempts to collate those experimental studies on medicinal plants and plant derived natural products with fluoride toxicity ameliorative effects. Literature scrutiny was performed by using online bibliographic databases and the studies for the last 15 years were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 25 medicinal plants and 17 natural products exhibited significant protection from fluoride toxicity in experimental animal models i.e., preclinical studies. Two clinical studies on medicinal plants were also found in literature showing beneficial yet poorly correlated outcome. Relevant research in this field could lead to development of a potentially useful agent in therapeutic management of fluoride toxicity in humans.

Fluoride Contamination of Groundwater from Semi-Arid Regions of Western India

A study on fluoride risk assessment was carried out in the semi-arid region of North Gujarat, India. The intricate link between groundwater fluoride and human health, lack of awareness, limited access to fluoride treatment facilities, and poor socio-economic conditions of the ~5.0 million rural population in the studied region make them vulnerable to fluoride. This study aimed to evaluate non-carcinogenic health risk, its severity, and the total population at risk in these regions due to chronic fluoride exposure. Fluoride in our samples (n=132) exhibits large spatial variability, and it ranges from ~0.13-8.64 mg.L-1 (average: 1.64 ± 1.50 mg.L-1) and 43% of them are more than the WHO limit of 1.5 mg.L-1. Hazard Quotient (HQ) was used to assess health risks through the ingestion exposure route. The comparison of the range (0.1-8.55 versus 0.06-4.11), average (1.63 ± 1.49 versus 0.78 ± 0.72), and median (1.26 versus 0.60) of HQ between children and adults highlights that the former are at more risk compared to latter. Our conservative estimates suggest that ~0.45 million children and ~1.06 million adult population, ~55% and ~20% of the respective population classes, of the region, are potentially at risk. The empirical Bayesian Kriging model was used to produce risk-assessments maps. These can help policymakers in prioritizing the application of mitigation funding and resources, and in increasing testing efforts in high-risk areas. We believe this study should guide policymakers to adopt strategies in ensuring the public health safety of the rural population, children in particular, of the studied region.

Receiver Operating Curve (ROC) analysis for fluorosis using simple blood parameter neutrophil lymphocyte ratio

The study aims to assess the preclinical stage of fluorosis i.e. Non skeletal fluorosis in human populations using a simple blood parameter, Neutrophil Lymphocyte Ratio as a predictive tool and includes different fluorosis categories (Dental, Skeletal & Non skeletal) surveyed out in the endemic villages and compared with the control population of non endemic area. Study Populations belonging to endemic villages Kowataal, Fulsar, Mahuapaani, Korbi and Amatikra within the block Podi uproda, distt. Korba situated in Chhattisgarh state of central India were cross sectionally studied. Segregation was done on the basis of Suspect (non-symptomatic) and Confirmed (Dental and Skeletal) cases of fluorosis and neutrophil to lymphocyte ratio calculated. A total 180 individuals were included in the study, out of which 67.33 % were confirmed cases of fluorosis. A significant decline in neutrophil to lymphocyte ratio was observed upon chronic fluoride ingestion. In the Receiver Operating Characteristic curve analysis of obtained NL ratios, the overall cut off value for fluorosis was obtained as ≤ 2.379 in the selected endemic region irrespective of symptoms of fluorosis i.e. dental or skeletal. The results concluding that The NL ratio can be used as a simple parameter for preclinical identification of fluorosis in fluoride exposed populations. However, urine and blood fluoride analyses of the subjects are also needed for further confirmation.

Changes in diabetic and renal profile of people exposed to fluoride in south India.

Type 2 Diabetes Mellitus is leading cause of Diabetic microvascular complications. India stands second across the globe in prevalence of diabetes mellitus. Due to deficit rain fall, the water table is exposed to more of salts and minerals from the rocks underground. One of the minerals is the Fluoride. Fluoride in negligible amount is good for dental health, chronic exposure to higher range of fluoride causes various metabolic disturbances. Aim: To study the effect of chronic fluoride exposure on diabetes mellitus. A total of 288 study subjects were recruited. The blood samples and urine samples were collected from all the study subjects. Study groups; Group1: Healthy Controls, Group2: Type 2 Diabetes Mellitus and Group3: Diabetic Nephropathy. The serum (0.313± 0.154) and urine (0.3±0.6) fluoride values of diabetic nephropathy group were significantly decreased in comparison between groups. The primary objective of the fluoride with insulin (-0.06) levels are inversely correlating and fluoride with microalbumin (0.083) levels are directly correlating. Results of the study gave a clear picture of effect of fluoride on insulin action and renal damage. In conclusion, though there is no significant effect of fluoride on FBS, PPBS and HbA1c, insulin is the determining factor for glucose homeostasis which is decreased. Microalbumin is yet another marker for renal clearance which is increased. Therefore, fluoride shall be considered as a parameter in prognosis of metabolic disorder especially Diabetes mellitus in fluoride endemic areas.

Radiological Findings More Important and Reliable in the Diagnosis of Skeletal Fluorosis

Skeletal fluorosis is the resultant of prolonged chronic fluoride exposure through fluoride containing water and food and /or industrial fluoride emission. In this disease, due to pathological changes in various bones of the body, many types of physical deformities develop which are more painful and unbearable. These bony deformities remain in man throughout his life. There is no cure available for these fluoride-induced disorders yet. Among these deformities, the most common bone deformities in humans are bending at the waist (kyphosis) and curvature of the lower extremities (genu-varum and genu-valgum). In severe state of skeletal fluorosis, neurological complications such as paraplegia and quadriplegia are also prevalent in human population. In fact, these are the crippling deformities and can be easily recognised by necked eyes. But many times mistakes are made in identifying skeletal fluorosis in its early stages. However, radiological study makes the diagnosis of skeletal fluorosis easier, which is also more important and reliable. Because even mild fluorideborne effects, such as periosteal exostosis, osteosclerosis, osteoporosis, and osteophytosis can be easily detected in X-rays of diverse bones of skeletal. However, the presence of fluoride-induced calcification of the interosseous membrane between radius and ulna bones of upper limbs or forearms is the most ideal or correct diagnostic feature or sign of skeletal fluorosis. In present editorial, besides the different forms of crippling deformities, various fluorideinduced radiological changes in diverse bones of subjects afflicted with mild to severe skeletal fluorosis have also been focussed which are more important, useful, and reliable in the diagnosis of skeletal fluorosis in humans.

Experimental study of the specificity of morphological changes development in internal organs with prolonged exposure to coal-rock dust and sodium fluoride to the body

Introduction. Occupational diseases detected at occupational examinations - pneumoconiosis and fluorosis - are, as a rule, chronic, the initial stages of development are almost asymptomatic. Industrial dust affects only the respiratory organs. Specific sign of fluoride intoxication is a lesion of the musculoskeletal system. The information available in the literature on the systemic manifestations of these diseases is not numerous. In this regard, it is relevant to study the early morphological changes, the timing of their occurrence and the features of development, depending on the specificity of the production factor. The study aims to experimentally identify the specificity of the development of morphological changes in organs and tissues under prolonged exposure to harmful production factors: coal-rock dust and sodium fluoride. Materials and methods. The authors conducted studies on adult white male laboratory rats. Scientists studied the features of the development of morphological changes in the bronchopulmonary system, heart, liver and kidneys in the dynamics of the impact of production factors on experimental models of anthracosilicosis and chronic fluoride intoxication. For histological examination, specialists carried out organ sampling in animals after 1, 3, 6, 9, 12 weeks of the experime Results. Chronic exposure to coal-rock dust, as well as sodium fluoride, leads to the development of compensatory and adaptive changes in the internal organs in the early stages of the experiment before the formation of degenerative and fibroplastic disorders of the stromal and parenchymal components in the later stages. Inhalation of coal-rock dust creates in experimental animals by an early breakdown of the adaptive mechanisms of the respiratory system and heart muscle. There is a formation from the 6th week of the experiment of pneumosclerosis with the spread to the air-conducting structures, atrophy of the bronchial mucosa, degenerative changes in cardiomyocytes. Despite the early formation of stroma fibrosis, reparative processes restrain dystrophic cell changes in the liver and kidneys. All this develops by the 9th week of the experiment. The accumulation of sodium fluoride leads to the early formation of pronounced protein dystrophy of the liver and kidney parenchyma with the development of necrotic changes by the 6-9 weeks of the experiment. Disorders in the bronchopulmonary system before the 9th week of exposure are of the nature of immune inflammation with the subsequent development of degenerative changes in the air-conducting structures. The heart has moderate dystrophy throughout the experiment. Regardless of the influencing factor, changes in the vessels of the studied organs at the initial stages of the experiment lead to hypertrophy of smooth muscle cells of the media and intima, followed by the development of endotheliosis and hyalinosis. Limitations. The results of the histological examination are descriptive of pathomorphological changes in the bronchopulmonary system, heart muscle, liver and kidneys. We did not conduct a morphometry of various structures of the studied organs has not been carried out with subsequent statistical processing of the results obtained. In this regard, when studying the specifics of the development of morphological changes depending on the influencing harmful production factor, the compared indicators were the first morphological changes and the timing of their formation. Conclusions. The obtained results have theoretical and practical significance for the development of recommendations for timely preventive and organ-specific therapeutic measures in the premorbid period of the development of occupational diseases. Ethics. The researchers conducted maintenance, feeding and removal of animals from the experiment in accordance with the requirements of the Order of the Ministry of Health of the Russian Federation "On approval of the Rules of Good Laboratory Practice" (No. 199n of 01.04.2016), as well as the Guide for the Maintenance and Use of Laboratory Animals (Guide for the Care and Use of Laboratory Animals, 1996). Scientists received permission from the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases to conduct the study.

THE ROLE OF AP-1 TRANSCRIPTION FACTOR ACTIVATION IN THE CHANGES OF PRODUCTION AND UTILIZATION OF NITRIC OXIDE IN THE GASTRIC MUCOSA OF RATS UNDER CONDITIONS OF CHRONIC FLUORIDE INTOXICATION

Millions of people are affected by excessive fluoride intake. The effect of fluorides on the activation or inhibition of redox-sensitive transcription factors remains poorly understood. The aim of this research is to examine the effect of activation of the transcription factor AP-1 on changes in the activity of inducible NO synthase and constitutive isoforms of NO synthase, concentrations of peroxynitrites of alkali and alkaline earth metals, concentrations of nitrites and nitrosothiols in the gastric mucosa of rats under conditions of chronic fluoride intoxication. The study was conducted on 18 adult male Wistar rats weighing 220-260 g. Experimental animals were randomly divided into 3 groups of 6 animals each: control, chronic fluoride intoxication group and AP-1 transcription factor blockade group. Chronic fluoride intoxication was simulated by the administration of sodium fluoride at a dose of 10 mg / kg for 30 days. AP-1 blockade was performed by administering SR11302 at a rate of 15 mg / kg twice a week. In the gastric mucosa, the following was studied: the activities of constitutive and inducible isoforms of NO synthase, the concentration of nitrites, peroxynitrites and nitrosothiols. Chronic fluoride intoxication reduces the activity of constitutive NO synthases by 37.73% and increases the activity of inducible NO synthase by 1.61 times. The concentration of peroxynitrites increases by 2.68 times, nitrites – by 1.74 times, and nitrosothiols – by 1.88 times. Blockade of AP-1 reduces the activity of inducible isoform by 2.11, does not affect the activity of constitutive isoforms, and reduces the concentration of peroxynitrites by 1.98 times, nitrites – by 2.10 times, and nitrosothiols – by 2.37 times. Activation of the transcription factor AP-1 under conditions of chronic excessive fluoride intake leads to increased production of nitric oxide in the gastric mucosa of rats, enhances its oxidation to nitrites, promotes the formation of nitrosyl groups in the reaction with low molecular weight donors of thiol groups and increases the peroxidation of nitric oxide with the formation of peroxynitrite.

Associations Between Essential Elements in Fingernails and Bone Quality in Populations Exposed to Chronic Fluoride in Drinking Water

Associations Between Essential Elements in Fingernails and Bone Quality in Populations Exposed to Chronic Fluoride in Drinking Water

The Diagnosis and Prevention of Fluorosis in Humans

Chronic fluoride intoxication in the form of fluorosis is a worldwide health problem and endemic at least in 25 countries. The principal cause of fluorosis in humans is the prolonged exposure of fluoride through drinking of fluoridated water. However, industrial fluoride emission and fluoride containing foods are also potential sources of fluoride exposures for the genesis of fluorosis. As per guidelines of the World Health Organization (WHO) fluoride content in the drinking water should not be higher than 1.5 mg/L (ppm). Above this limit of fluoride in drinking water, it becomes toxic and injurious for human health and causes diverse deformities in teeth and bones. In humans, basically three forms of fluorosis namely dental, skeletal and non-skeletal fluorosis have been recognised. The diagnosis of fluoride intoxication (fluorosis) in humans is made on the basis of history, clinical or pathognomonic signs and testing of biological samples. The current status of endemic fluorosis could be assessed by estimation of fluoride in the blood serum and urine. The presence of dental mottling and calcification of interosseous membrane on a forearm radiograph may be helpful in the diagnosis of dental and skeletal fluorosis, respectively. For the prevention of fluorosis, fluoride free drinking water and food items, diet having ample amount of nutrients, general awakening in people and collective efforts are important and highly needed. This editorial will be useful for researchers and health workers in the diagnosis and prevention of fluorosis in humans, respectively.

Impact of Chronic Sodium Fluoride Toxicity on Antioxidant Capacity, Biochemical Parameters, and Histomorphology in Cardiac, Hepatic, and Renal Tissues of Wistar Rats.

The study was designed to determine the fluoride distribution after its oral exposure in drinking water and its associated impact on biochemical, antioxidant markers and histology in the liver, kidney, and heart of male Wistar rats. On 100ppm exposure, the highest accretion of fluoride occurred in the liver followed by the kidney and heart. Fluoride exposure significantly (p˂0.05) increased the plasma levels of dehydrogenase, aminotransferases, kidney injury molecule-1 (KIM-1), and other plasma renal biomarkers but decreased the levels of total plasma proteins and albumin in a dose-dependent manner. Reduction (p˂0.05) in the activities of antioxidant enzymes viz. acetylcholinesterase, arylesterase, superoxide dismutase, catalase, glutathione peroxidase, and reductase with increased levels of protein and lipid peroxidation was recorded in the liver, kidney, and heart of fluoride-administered rats. Fluoride exposure (100ppm) induced lipid peroxidation was highest in kidney (4.4 times) followed by liver (2.6 times) and heart (2.5 times) and as compared to their respective control. The percent rise in protein oxidation at 30% was almost equal in the kidney and liver but was 21.5% in the heart as compared to control. The histopathological alterations observed included congestion and hemorrhage along with degeneration and necrosis of parenchymal cells in hepato-renal tissues and myocardium, severity of which varied in a dose-dependent manner. Taken together, fluoride distribution in the liver, heart, and kidney after chronic fluoride intake correlated well with fluoride-induced hepatic and cardio-renal toxicity in a concentration-dependent manner. These results draw attention that chronic fluoride intake pose a significant health risk for human and animal residents of fluoride endemic areas.

A Brief and Critical Review of Chronic Fluoride Poisoning (Fluorosis) in Domesticated Water Buffaloes (Bubalus bubalis) in India: Focus on its Impact on Rural Economy

In the rural areas of India, fluoridated drinking water, industrial fluoride pollution and fluoride-rich feed phosphate supplements are the major sources of fluoride exposure for domesticated water buffaloes (Bubalus bubalis). However, the fluoridated drinking groundwater is the commonest and principal source of fluoride exposure for these ruminants. Chronic fluoride exposure for long-time deteriorate the animal health and causes the fluorosis disease. In the country, the drinking groundwater sources of villages are contaminated with fluoride beyond the threshold value, 1.0 or 1.5 mg/L. At 1.5-1.7 ppm fluoride concentration in drinking water, 62.2% and 21.6% calves and 55.9% and 48.3% adult buffaloes are found to be afflicted with dental and skeletal fluorosis, respectively. The maximum prevalence of dental and skeletal fluorosis, 96.8% and 34.4% in calves and 66.9% and 60.2% in adult buffaloes has also been reported at or > 3.0 ppm fluoride in drinking water, respectively. However, calves are found to be more sensitive and susceptible to chronic fluoride toxicity or fluorosis. Besides the deterioration of the animal health, chronic fluoride intoxication in buffaloes also weakens the rural economy which has been focussed in the present review. In this communication, besides the status of chronic fluoride intoxication in the form of osteo-dental and non-skeletal fluorosis in buffaloes, determinations, bio-indicators and bio-markers of fluorosis and prevention and control of chronic fluoride poisoning in these animals are also considered and briefly and critically reviewed. Simultaneously, research gaps are also identified and highlighted them for further research study on chronic fluoride intoxication in buffaloes. Findings of this review may help in preparation of health policy for improving the health and mitigation of fluorosis in economically important buffalo animals in the country.

Fluoride sensitivity in freshwater snail, Bellamya bengalensis (Lamarck, 1882): An integrative biomarker response assessment of behavioral indices, oxygen consumption, haemocyte and tissue protein levels under environmentally relevant exposure concentrations

There is limited information on fluoride toxicity and risk overview on ecotoxicological risks to aquatic invertebrate populations particularly molluscan taxa. This necessitated the assessment of toxicity responses in the freshwater snail, Bellamya bengalensis exposed to environmentally relevant concentrations of sodium fluoride. Under lethal exposures (150, 200, 250, 300, 400 and 450 mg/l), the median lethal concentrations (LC50) were determined to be 422.36, 347.10, 333.33 and 273.24 mg/l for B. bengalensis at 24, 48, 72 and 96 h respectively. The rate of mortality of the snails was increased significantly with elevated concentrations of the toxicant. The magnitude of toxicity i.e., toxicity factor at different time scale was also higher with increased exposure duration. Altered behavioural changes i.e., crawling movement, tentacle movement, clumping tendency, touch reflex and mucous secretion in exposed snail with elevated concentrations and exposure duration. Similarly, oxygen consumption rate of the treated snail also lowered significantly during 72 and 96 h of exposure. Under 30-day chronic exposures (Control-0.00 mg/L; T1–27.324 mg/L; T2–54.648 mg/L), protein concentrations in gonad and hepatopancreas of exposure groups was significantly lowered. Chronic exposures also revealed lowered haemocytes counts in exposure groups. The potential for loss of coordination, respiratory distress and physiological disruption in organisms exposed to environmentally relevant concentrations of fluoride was demonstrated by this study. The estimation and magnitude of toxicity responses are necessary for a more accurate estimation of ecological risks to molluscan taxa and invertebrate populations under acute and chronic fluoride exposures in the wild.

ROLE OF ΚB AND AP-1 TRANSCRIPTION FACTORS IN CHANGES IN NITRIC OXIDE PRODUCTION AND UTILIZATION IN THE HEART OF RATS UNDER CHRONIC FLUORIDE INTOXICATION

Fluorides, being hazardous contaminants of soil and drinking water, can get in excessive amounts into human and animal bodies. This is especially true for regions where the fluoride content in soils is very high, for example, Poltava, Dnipropetrovsk, and Kirovohrad regions in Ukraine. Excessive fluoride intake can change the rate of nitric oxide production. The impact of fluorides on changes in nitric oxide production and metabolism in the heart and the role of redox-sensitive transcription factors in these changes are poorly understood. The aim of this study was to determine the effect of activation of κB transcription factors and activator protein 1 on the activity of inducible NO-synthase, constitutive isoforms of NO-synthase, nitrite and nitrate reductase, arginase, concentration of nitrites, peroxynitrite and nitrosothiols in the heart of rats during chronic fluoride intoxication. Materials and methods. The study was performed on 24 adult male Wistar rats weighing 220-260 grams. Animals were randomly divided into 4 groups of 6 animals in each (control, chronic fluoride intoxication group, κB blockade group and activator protein 1 blockade group). The experiment lasted 30 days. We determined the activity of inducible NO-synthase, constitutive isoforms of NO-synthase, the concentration of peroxynitrite alkali and alkaline earth metals, the concentration of nitrites and nitrosothiols, the activity of nitrite reductase, nitrate reductase and arginase. Results. Chronic fluoride intoxication increases the activity of inducible NO-synthase by 1.74 times, does not affect the activity of constitutive isoforms and reduces the activity of arginase by 35.68% compared with the control group of animals. The concentration of nitrites in the heart of rats increases 1.73 times, peroxynitrite 1.43 times, and the concentration of nitrosothiols doubled. The use of κB transcription factor blockers and activator protein 1 reduces nitric oxide production from NO synthases and reduces the concentrations of all nitric oxide metabolites in the heart of rats under conditions of chronic fluoride intoxication. Conclusions. Activation of κB transcription factors and activator protein 1 during chronic excessive intake of fluoride leads to hyperproduction of nitric oxide in the heart of rats due to increased activity of inducible NO-synthase and nitrite reductases. Excess production of nitric oxide under chronic fluoride intoxication leads to the accumulation of nitrites, peroxynitrite and nitrosothiols in the heart of rats.

Association Between Osteoarthritis and Water Fluoride Among Tongyu Residents, China, 2019: a Case-Control of Population-Based Study.

Fluoride is an environmental chemical that has adverse effects on articular cartilage, probably increasing osteoarthritis (OA) risk. However, this association still needs more epidemiological evidence to clarify. The aim of this study was to determine the relationships between chronic fluoride exposure and OA risk among the residents living in Tongyu County, China, 2019, with a frequency-matched case-control study (186 OA patients and 186 healthy participants). The results showed that urinary fluoride (UF) (2.73 ± 1.18mg/L) was significantly higher in OA patients compared to the controls (2.35 ± 1.24mg/L) (p < 0.002). After adjustment, the odds ratios (ORs) with 95% confidence intervals (95% CIs) between the OA risk and fluoride were calculated by the unconditional logistic regression. In full sample analysis, a 1mg/L increase in UF level was associated with a 27% higher risk of OA (1.06-1.52, p = 0.008), and 4th quarter's participants were associated with higher risk when compared to 1st quarter (OR: 2.46, 95% CI: 1.34-4.57, p = 0.003). In stratified analysis, compared to 1st quarter, 4th quarter's participants were 4 times more likely to have OA (1.86-8.82, p < 0.001) in the non-obese group and 7.7 times more likely to have OA (2.58-25.05, p < 0.001) among adults ≤ 60years. In conclusion, excessive exposure of water fluoride may increase OA risk, and could have more impact on the specific population such as non-obese, and adult aged ≤ 60years.

Early childhood fluoride exposure and preadolescent kidney function

BackgroundEarly-life renal maturation is susceptible to nephrotoxic environmental chemicals. Given the widespread consumption of fluoride and the global obesity epidemic, our main aim was to determine whether childhood fluoride exposure adversely affects kidney function in preadolescence, and if adiposity status modifies this association. MethodsOur study included 438 children from the PROGRESS cohort. Urinary fluoride (uF) was assessed at age 4 by diffusion analysis; outcomes studied included estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), selected kidney proteins and blood pressure measured at age 8–12 years. We modeled the relationship between uF and outcomes, and adjusted for body mass index (BMI), age, sex, and socioeconomic status. ResultsThe median uF concentration was 0.67 μg/mL. We observed null associations between 4-year uF and preadolescent eGFR, although effect estimates were in the expected inverse direction. A single unit increase in ln-transformed uF was associated with a 2.2 mL/min decrease in cystatin C-based eGFR (95% CI: 5.8, 1.4; p = 0.23). We observed no evidence of sex-specific effects or effect modification by BMI status. Although uF was not associated with BMI, among children with obesity, we observed an inverse association (β: 4.8; 95% CI: 10.2, 0.6; p = 0.08) between uF and eGFR. ConclusionsLow-level fluoride exposure in early childhood was not associated with renal function in preadolescence. However, given the adverse outcomes of chronic fluoride consumption it is possible that the preadolescent age was too young to observe any effects. Longitudinal follow-up in this cohort and others is an important next step.

The potential risks of chronic fluoride exposure on nephrotoxic via altering glucolipid metabolism and activating autophagy and apoptosis in ducks

Fluoride is one of the most widely distributed elements in nature, while some fluorine-containing compounds are toxic to several vertebrates at certain levels. The current study was performed to evaluate the nephrotoxic effects of fluoride exposure in ducks. The results showed that the renal index was decreased in NaF group, and fluoride exposure significantly decreased the levels of serum Albumin, Glucose, Total cholesterol, Urea, protein and Triglycerides, confirming that NaF exhibited adverse effects on the kidney. The overall structure of renal cells showed damage with the signs of nuclelytic, vacuolar degeneration, atrophy, renal cystic cavity widening after fluoride induction. Renal vascular growth was impaired as the expression of VEGF and HIF-1α decreased (p > 0.05). More importantly, autophagy and apoptosis levels of CYT C, LC3, p62, Beclin, M-TOR, Bax and Caspase-3 were increased (p < 0.05) in the NaF treated group. Interestingly, our results showed that Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC) activated the M-TOR autophagy pathway. Meanwhile, the PE acted on Atg5/ LC3 autophagy factor, followed by the auto-phagosome generation and activation of cell autophagy. These results indicate that NaF exposure to duck induced nephron-toxicity by activating autophagy, apoptosis and glucolipid metabolism pathways, which suggest that fluorine exposure poses a risk of poisoning.

Problems of formation of the toxic hepatopathy forming in the conditions of chronic fluoride intoxication of the body

Introduction. Aluminium production is characterized by the accumulation of impurities of various toxic and chemical compositions in the air of working areas, the predominant among which are fluoride compounds. The accumulation of fluorides in the body causes the development of osteoarticular and associated systemic pathology. The aim of the study was to evaluate the hygienic and medico-biological features of toxic liver damage in the conditions of chronic fluoride intoxication of the body. Material and methods. The hygienic working conditions of the workers of the primary professions in aluminium production were evaluated. The analysis of hepatobiliary dysfunction based on clinical and instrumental methods was carried out in 263 subjects with fluoride intoxication and a comparison group of 116 persons. Experimental studies of the morpho-functional liver state in modelling chronic fluoride intoxication were carried out based on toxicological, biochemical, pathomorphological methods with histological analysis of tissues. The toxic properties of sodium fluoride were studied in 117 white laboratory male rats with its peroral route intake into the body. Results. The qualitative composition of the air in the working areas in the electrolysis building was analyzed. The prevalence of pathological disorders of the biliary tract in metallurgists engaged in aluminium production was assessed. Clinical studies revealed a significant prevalence of toxic fluoride hepatopathy, fatty hepatosis, cholecystitis and other disorders in the group of patients with chronic fluoride intoxication. The harmful effect of sodium fluoride on hepatocytes, vessels of the portal tract was shown in an experiment. Hyperfunction of the reticuloendothelial system, Kupffer cell proliferation, irreversible destruction of hepatocytes, necrosis against the background of severe dystrophy, and decreased synthetic activity of the liver were determined. Conclusion. The structure of occupational diseases in the workers engaged in the aluminium production is dominated by hepatobiliary pathology caused by toxic liver damage with fluoride confirmed by experimental data on destructive violations of its morphostructure.

A Case of Fluorosis: Fluoride-Induced Osteopetrosis

There are multiple etiologies of increased bone density, including osteopetrosis and fluorosis. Osteopetrosis can either be a malignant autosomal recessive condition found in children or a benign autosomal dominant adult variant; both of which are characterized by decreased bone resorption. In contrast, fluorosis is characterized by increased bone formation secondary to chronic fluoride intoxication, but with a similar clinical manifestations to osteopetrosis.A 70-year-old lady with generalized joint aches, stiffness as well as fatigue, was found to have high bone mineral density and alarmingly high fluoride levels. The patient was found to be drinking fluoride containing water from an untreated local well for many years.Fluorosis results in increased bone mineral density and disease progression correlates with length of exposure. Fluorosis can result in reversible musculocutaneous symptoms and radiological findings. However, severe chronic cases may develop irreversible neurologic manifestations. Urinary fluoride testing is the screening modality of choice, and the key component of management is avoidance of the source of fluoride intoxication as well as monitoring of urinary fluoride levels.