Chronic Fluoride Intoxication Research Articles

Changes in autonomic regulation in workers under conditions of long-term fluoride intoxication

Introduction. Long-term intake and accumulation of fluoride compounds in the body, in addition to pathological changes in the bronchopulmonary system, bone tissue, liver, leads to changes in the regulatory systems, primarily the autonomic ones, in the conditions of chronic fluoride intoxication. The aim of the study was to assess the nature and severity of the changes in autonomic regulation in workers of the main occupations in aluminum production under exposure to chronic fluoride intoxication. Material and methods. We examined fifty two male workers of aluminum production over the age range from 40 to 56 years; work experience was more than 15 years. Autonomic regulation was assessed using spectral analysis of the heart rate variability, highlighting oscillations in the ranges of very low frequency (0.004–0.08 Hz), low (0.09–0.16 Hz), and high frequencies (0.17–0.5 Hz). Results. Analysis of the heart rate variability made it possible to identify 4 groups of subjects: 16 individuals had a moderate decrease in variability and a predominance of low-frequency oscillations, 12 subjects examined cases had a pronounced decline in variability in all frequency ranges; a decrease in the capabilities of autonomic regulation was manifested during a test with hyperventilation by an increase in very low frequency oscillations frequency indicating the need for activation of suprasegmental autonomic centers. In 24 subjects, the stable predominance of low-frequency oscillations indicates an enhancement in sympathetic influence. In response to the hyperventilation test, most of them (18 subjects were included in the group 3) showed an increase in low and very low frequency oscillations as a sign of a violation of baroreceptor regulation. Limitations. The study was limited by the number of workers with long-term work experience in aluminum production who underwent an in-depth medical examination. Conclusion. Changes in autonomic regulation are observed in the majority of aluminum production workers with long-term work experience, which gives grounds to recommend a study of neurovegetative status using heart rate variability analysis during preventive examinations to identify individuals at high risk of developing comorbid diseases.

Associations of the variable site rs2010963 of the VEGF-A gene with multifocal atherosclerosis in aluminum industry workers with chronic occupational intoxication with fluoride compounds

Introduction. The aluminum industry occupies a leading position among non-ferrous metallurgy industries in revealing somatic pathologies in workers that occur against the background of chronic fluoride intoxication. Long-term exposure to fluorides on the body has a cardiovasotoxic effect, leads to structural and functional disorders of the myocardium and the development of comorbid cardiovascular pathology. This dictates the need for a risk-oriented approach to its diagnosis, including one based on molecular genetic analysis, for the timely identification of risk groups for the development of atherosclerosis and the elaboration of preventive measures aimed at preserving the health and maintaining working longevity of the studied occupational cohort. Materials and methods. There were examined ninety seven metallurgists with a previously proven diagnosis of chronic occupational intoxication with fluoride compounds, engaged in aluminum production. The comparison group consisted of 33 workers of this enterprise without a proven occupational disease. All respondents underwent ultrasound investigation of the main arteries. Genotyping of the rs2010963 polymorphic locus of the VEGF-A gene was carried out in a 96-well format using TaqMan technology (allele-specific real-time PCR). Results. The associative connection of the G/G VEGF-A genotype is determined in metallurgists with the risk of developing chronic occupational intoxication with fluoride compounds and heterozygous G/C genotype in subjects with multifocal atherosclerosis. The high level of predictive value of the polymorphism -634 G/C (rs2010963) of the VEGF-A gene allows considering it a marker of the risk for the developing atherosclerosis in workers exposed to long-term impact to fluoride compounds on the body. Limitations. The study was limited to the number of long-term work experienced subjects undergoing periodic medical examinations and undergoing inpatient treatment at the Research Institute for Complex Problems of Hygiene and Occupational Diseases. Conclusion. It is recommended to conduct a screening molecular and genetic analysis in a clinical hospital setting for timely assessment of the prognostic significance of risk markers for the development of atherosclerosis and its complications in workers of basic occupations engaged in aluminum production.

HYDRO-TELLURIC FLUOROSIS IN MOROCCO: TOXICITY, FLUOROPATHY AND CURRENT STATE OF PREVENTIVE ASPECTS

Prolonged exposure to fluorides causes chronic fluoride intoxication in humans and animals, which the main manifestation is, osteodental fluorosis. In Morocco, fluorosis affects a large number of animals, particularly ruminants, and constitutes a serious handicap in contaminated regions, both economically and in terms of health. It is identified by a change in the color, structure and orientation of the teeth, and by a change in the structure and texture of the bones. Regardless of the animal species affected, fluorosis appears after a relatively long period of exposure, from several months to several years, by disorders of phosphocalcic metabolism resulting in osteodental changes associated with various general symptoms. These lesions compromise the grip, chewing and movement of the animals, and thus cause malnutrition, a drop in productivity and sometimes may lead to death. These disturbances have the characteristic of being irreversible, since once installed, no treatment allows to eliminate them in a definitive way, prevention is therefore the only way to alleviate. In order to face this fluoride intoxication, farmers use mainly empirical methods, such as transhumance, the purchase of animals from fluoride free zones or their sale at a young age before the appearance of dental lesions. The reduction of ingestion by using water sources and feed with low fluoride content as well as the supplementation of minerals (Al, Mg, B, Ca) and vitamins (the case of vitamin C) to limit absorption, are also practiced. However, aluminum-based licking salt blocks and supplemented feed enriched with minerals and vitamins are no longer used due to the lack of financial means of some breeders and state financial support. While the preventive effects of calcium, magnesium and boron, have still not been the subject of clinical studies in ruminants. Decidedly, the lack of vulgarization and the socio-economic level of the population, as well as the lack of financial support, constitute the main obstacles in the ultimate goal of counteracting hydrotelluric fluorosis.

Can People Get Fluorosis from Drinking Water from Surface Water Sources? Fluoride Test of Water Mandatory Before its Supply

It is true that the groundwater of most areas of the world is almost fluoridated with varying concentrations. There are many countries, including India, whose drinking groundwater contains fluoride more than the parameters set by World Health Organization (WHO) that is 1.5 ppm. Drinking such fluoridated water repeatedly and for a long time causes dangerous fluorosis disease in people. This disease remains life-long in people and there is no permanent cure till now. Thousands of people around the world are suffering from this disease. Generally, the water of surface water sources (puddles, rivers, canals, streams, lakes, ponds, dams, reservoirs, etc.) is considered to be free of fluoride. However, according to WHO, its quantity in the water of different surface water sources has been estimated from 0.01 to 0.3 ppm. But recent studies revealed that in many of these freshwater sources, the amount of fluoride was found to be more than 1.0 ppm or 1.5 ppm. If such water is used for drinking for long time, then the health of the people gets affected and there is a possibility of getting dreaded fluorosis disease. Due to fluorosis, people’s teeth become weak and discoloured (dental fluorosis) and their diverse skeletal bones become porous, weak, and deformed (skeletal fluorosis). People also become hunchbacked (kyphosis) and lame (crippling) for life due to this disease. Many health complaints such as gastrointestinal discomforts, polydipsia, polyuria, repeated abortion, impaired reproduction and endocrines, neurological disorders, etc. are also found in people afflicted with chronic fluoride intoxication. If animals also start drinking this water for a long time, then they also get this dangerous disease. In rural areas, this water is also used for agricultural irrigation which also causes serious anomalies in diverse species of agriculture crop plants and ultimately reduces annual agricultural yield. However, before supplying drinking water to the human population from any of surface water sources, the water of these sources must be tested for evidence of fluoride. From the point of view of health, if the amount of fluoride is found to be more than the prescribed parameters, the water supply of such water sources should not be done as far as possible. The present communication highlights various potential adverse consequences in humans from drinking water from surface water sources containing fluoride above the permissible or acceptable limit or level.

Study of glutathione-S-transferase (GST) T1 and M1 genes in aluminum industry workers with comorbid cardiovascular pathology

Introduction. Employees of the main professions of aluminum production have a high level of professional and production-related pathology, primarily diseases of the circulatory system associated with the long-term influence of vasotoxic factors on the body. The pathogenetic course of angiopathies does not proceed in isolation, it is predetermined by chronic fluoride intoxication and hereditary component. The establishment of associations determined on the basis of studying the polymorphism of glutathione-S-transferase genes with the risk of developing comorbid cardiovascular pathology makes it possible to use genetic analysis in its early diagnosis.
 The study aims to explore the polymorphism of GST genes in aluminum industry workers with comorbid cardiovascular pathology.
 Materials and methods. The authors have carried out the study using clinical and molecular genetic diagnostic methods in workers of the main professions engaged in the production of aluminum, with chronic occupational intoxication with fluorine compounds and persons with individual signs of fluoride exposure to the skeleton (comparison group). By detecting extended deletions in the loci of the GSTT1 and GSTM1 genes, the researchers have assessed the association of the studied genotypes with the risk of chronic intoxication and atherosclerosis.
 Results. In the cohort of patients (36.58%) and in the comparison group (16.98%), the authors have revealed a combined form of cardiomyopathy complicated by coronary atherosclerosis, coronary heart disease. Also, scientists have established significant differences in the frequency distribution of genotypes of GST genes. Homozygous polymorphism GSTT1 0/0 is a risk factor for the development of occupational pathology against the background of the predominance of the normal genotype GSTM1+. Predictors (GSTT1 0/0, GSTM1 0/0) of the risk of atherosclerosis associated with hypertension in persons with chronic fluoride intoxication were determined.
 Conclusion. The association of GST genes with the development of comorbid cardiovascular pathology was determined in the structure of professional and production-related pathology in aluminum industry workers.
 Ethics. We have conducted the study of employees at the aluminum plant on a voluntary basis with the written consent of the examined persons on the basis of a specialized clinic of the Research Institute of Complex Problems of Hygiene and Occupational Diseases in accordance with the Ethical principles of conducting scientific and medical research with human participation ("Rules of Clinical Practice in the Russian Federation", Order of the Ministry of Health of the Russian Federation No. 266, 2003; Helsinki Declaration of the World Medical Association "Ethical principles of conducting scientific medical research with human participation", 2013).

Pathogenesis of morphological changes in organs and tissues in chronic fluoride intoxication (literature review)

Introduction. Traditionally, the main manifestation of chronic fluoride intoxication is the damage to the skeletal system, while during recent years a large amount of works has been accumulated on the study of the mechanism of action of both fluorine and its compounds on non-skeletal tissues. Based on the analysis of the Russian Science Citation Index, PubMed, Scopus, Web of Science, MedLine, Google Scholar, CyberLeninka databases, a review of contemporary concepts of morphological changes in organs and systems under the conditions of long-term exposure to fluorine compounds is presented.
 Effect of fluorine on the musculoskeletal system. Fluorine Ihas been shown to induce differentiation and apoptosis of osteoblasts and osteoclasts, leading to various skeletal injuries. Active osteogenesis and accelerated bone metabolism are key processes in the progression of skeletal fluorosis and the pathological base of the diversity of osteogenic lesions.
 Effect of fluorine on non-skeletal tissues. Data on the effect of fluorine on the induction of free radical oxidation in the cerebral cortex, redistribution, and damage to nerve cells are presented. Activation of apoptosis, oxidative stress, and a decrease in the activity of antioxidant enzymes under the influence of sodium fluoride in the heart muscle are shown, data on the development of functional and structural disorders in the myocardium are given. Due to fluoride intoxication, the formation of degenerative and inflammatory changes in the respiratory system, liver, and kidneys, structural disorders and dysfunction of the thyroid gland, as well as an increase in the level of reactive oxygen species and the induction of apoptosis in these organs are shown. Data on the effect of sodium fluoride on the histological structure of the reproductive organs with a decrease in sperm motility, lack of differentiation and maturation of spermatocytes, intensification of free radical oxidation and cell apoptosis are presented.
 Conclusion. The analysis carried out allows expanding the understanding of the pathogenetic bases of morphological changes and functional failure of organs and tissues under the conditions of chronic fluoride intoxication, to substantiate a systemic, integrated approach to its treatment and prevention.

Experimental study of morphological changes in the heart and blood vessels in the course of chronic fluoride intoxication

Introduction. Clinical studies have shown the development of a complex of non-specific changes in internal organs due to chronic fluoride intoxication. The accumulation of fluorine in the body initiates free radical oxidation, promotes the development of pathological processes in the heart against the background of an imbalance between pro- and antioxidants, and vascular endothelial dysfunction. Pathological activation of intima cells leads to unbalanced production of damaging factors, changes in the hemostasis system, and entails morphological and functional disorders of organs.
 Materials and methods. The experiments were carried out on one hundred twenty white male rats. A morphological study of the heart, blood vessels was performed out at 1, 3, 6, 9 and 12 weeks of chronic fluoride intoxication.
 Results. The 1st-3rd weeks of the experiment are characterized by the preservation of the morphological structure of the cardiac muscle against the background of the previously shown a compensatory activation of the components of the redox-signalling system, which provided a decrease in the intensity of free radical processes. With an increase in the duration of exposure to sodium fluoride (6–9 weeks) these mechanisms failure was noted, which was manifested by the development of degenerative changes in the myocardium, progressing up to the 12th week of the experiment. The described changes correlated with the development of endotheliosis, degenerative and fibroplastic processes, circulatory disorders in the vessels of the heart and other organs.
 Limitations. Histological findings are descriptive.
 Conclusion. The results obtained are of practical importance for the elaboration of effective methods for timely organ-protective prevention and correction of pathomorphological disorders, depending on the organ-specific features and duration of fluoride intoxication.

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).

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.

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.

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.

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.

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.

Clinical and experimental studies of the effect of chronic fluoride intoxication on the hormonal status of the body and morphological changes in the thyroid gland

Introduction. The systemic violation of the body's homeostasis under the conditions of the negative impact of production factors scientists determine by the mismatch of neurohumoral mechanisms of regulation of metabolic processes. There are endocrinopathies. They occur with disorganization of the metabolism and violation of the thyroid gland's functional activity with disorganization of the metabolism, infringement of the thyroid gland's available action. The study aimed to learn the nature of endocrine dysfunction, histological changes of the thyroid gland associated with the dynamics of chronic fluoride intoxication of the body. Materials and methods. We analyzed the state of bone tissue and assessed the degree of articular syndrome during the large-scale structural reconstruction of the skeleton in aluminum production workers. The scientists examined the workers using double photon densitometry. The researchers studied the metabolic parameters based on a range of biochemical and instrumental methods. The experiment involved sexually mature male white laboratory rats with a bodyweight of up to 300 grams. We analyzed hormonal status disorders with an assessment of the degree of morphological changes in the thyroid gland. Results. The researchers analyzed the severity of disorders of individual endocrine mechanisms of homeostasis regulation and thyroid morph structure in hyperfluorosis. We treat fluorosis as a polyfunctional pathology. A high proportion of endocrinopathies is a clinical syndrome. It increases the pathological course of chronic fluoride intoxication in workers. We confirm the study with experimental data on metabolic disorders with a persistent toxic effect. We revealed hyperfunction of the thyroid gland against the background of a decrease in glucocorticoid activity, stable electrolyte, and mineral shifts. The researchers conducted an experiment on the late stages of fluoride intoxication. Conclusions. Clinical studies of individuals with chronic fluoride intoxication and concomitant endocrinopathy revealed a significant increase in the number of workers with abdominal obesity, musculoskeletal disorders, mineral metabolism disorders. Also, with deforming osteoarthritis of the joints, osteoalgia against the background of thyroid insufficiency. Experimental data confirm this. The fluorine accumulation in the body causes multidirectional disorders of the hormonal mechanisms of regulation of metabolic processes, alternation of hypo- and hyperfunction changes in the thyroid gland associated with fluoride duration intoxication.

NF-kB-Mediated Shift in Activity in Macrophage Polarization Marker Enzymes in Rats’ Heart During Chronic Fluoride Intoxication

NF-kB-Mediated Shift in Activity in Macrophage Polarization Marker Enzymes in Rats’ Heart During Chronic Fluoride Intoxication

Role of NF-κB transcriptional factor activation during chronic fluoride intoxication in development of oxidative-nitrosative stress in rat’s gastric mucosa

Fluoride compounds are known as hazardous environmental pollutants that can enter the body with drinking water. Chronic exposure to fluoride leads to development of oxidative stress and can lead to activation of nuclear factor κB (NF-κB). The aim of this work is to clarify the role of NF-kB activation in production of reactive nitrogen and oxygen species, activity of antioxidant enzymes and intensity of lipid peroxidation (LPO) in gastric mucosa of rats during chronic fluoride intoxication. Materials and methodsWe carried out the study on 18 mature male rats of the Wistar line. The animals were divided into 3 groups: control animals (6), group of chronic fluoride intoxication (6), and animals (6), which received the NF-κB inhibitor, namely ammonium pyrrolidine dithiocarbamate (PDTC) in a dose of 76 mg / kg (iNF-κB group) during modeling of chronic fluoride intoxication. To assess the development of oxidative stress we studied superoxide production (O2-), activity of superoxide dismutase (SOD), catalase (CAT) and concentration of free malondialdehyde (MDA). We also assessed NO production and concentration of its metabolites (peroxynitrite, nitrosilated thiol groups, nitrites). ResultsChronic fluoride intoxication leads to NO hyperproduction with subsequent increase in concentration of its later metabolites (peroxynitrite, nitrosilated thiol groups, nitrites). Production of O2- increases, SOD activity decreases, CAT activity increases and MDA concentration also increases. Inhibition of NF-kB activation by PDTC normalizes the parameters studied. ConclusionsActivation of NF-κB during chronic fluoride intoxication leads to the development of hyperproduction of NO and development of oxidative-nitrosative stress.

ASSESSMENT OF THE EFFICIENCY OF PREVENTION OF CHRONIC FLUORINE INTOXICATION WITH RHODIOLA ROSEA L. ADAPTOGEN

Introduction. Fluorine and its compounds are industrial pollutants that cause the development of chronic fluorine intoxication (CFI) during long-term intake. It has been shown that in CFI there are disturbances in metabolic processes and morphological changes in various organs. Therefore, the search for organ protective prevention and correction of damage caused by CFI remains relevant in occupational health and medicine. The perspective direction is the assessment of the possibility of prevention and correction of CFI related disorders by means of the remedies of plant origin possessing adaptogenic action, one of which is Rhodiola Rosea L. The objective of the research. To evaluate the effectiveness of organ protective prevention of chronic fluoride intoxication with an adaptogenic drug-containing Rhodiola Rosea L in the experiment conditions Material and methods. The work was carried out on 45 white male rats weighing 200-250 g. Animals were divided into groups of 15 animals: control rats; rats with chronic exposure to sodium fluoride (NaF) for 12 weeks; rats who received NaF solution while administering of Rhodiola Rosea L. extract. Determination of biochemical indices of metabolism in blood serum and histologic studies of the organs (liver and kidneys) were performed. Results. The use of an adaptogenic drug-containing Rhodiola Rosea L. was shown to be effective in preventing the disorders caused by chronic exposure to fluorine compounds, since it normalizes oxidative metabolism in tissues, reduces the manifestation of degenerative, dystrophic and necrotic changes in the liver and kidneys, restores the synthetic and detoxication functions of the liver, and also preserves the homeostatic function of the kidneys. Conclusion. The use of an adaptogenic drug-containing Rhodiola Rosea L. for the prevention of damage caused by the chronic effects of fluorine compounds on the body is effective.

The intracellular mediation during chronic fluoride intoxication in rats

The intracellular mediation during chronic fluoride intoxication in rats