Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats.

Several studies have shown that acute fluoride (F(-)) exposure impairs cardiac function, but the molecular mechanism is not clear. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F(-) for 24 h. A significant accumulation of F(-) was found in the serum and myocardium of experimental rats. F(-) treatment causes myocardial necrosis as evident from increased levels of myocardial troponin I, creatine kinase, lactate dehydrogenase and aspartate transaminase. In addition, F(-) induces myocardial oxidative stress via increased reactive oxygen species, lipid peroxidation, protein carbonyl content and nitrate levels along with decreased in the levels of enzymatic (superoxide dismutase 2, catalase, glutathione peroxidase and glutathione s transferase pi class) and non-enzymatic (reduced glutathione) antioxidants. Notably, F(-) triggers myocardial apoptosis through altered Bax/Bcl2 ratio and increased cytochrome c, caspase 3p20 and terminal deoxynucleotidyl transferase dUTP nick end labeled positive cells. An increased cardiac expression of Nox4 and p38α MAPK in F(-) treated rats indicates the oxidative and apoptotic damage. Moreover, ultra-structural changes, histopathological and luxol fast blue staining demonstrates the degree of myocardial damage at subcellular level. Taken together, these findings reveal that acute F(-) exposure causes cardiac impairment by altering the expression of oxidative stress, apoptosis and necrotic markers.

Effect of fluoride on calcium ion concentration and expression of nuclear transcription factor kappa-B ρ65 in rat hippocampus.

The study investigated the neurotoxicity of drinking water fluorosis in rat hippocampus. Just weaning male Sprague-Dawley (SD) rats were given 15, 30, 60 mg/L NaF solution and tap water for 9 months. The calcium ion concentration ([Ca(2+)]) in synaptosomes was measured by double wavelength fluorescence spectrophotometer and the expression level of nuclear transcription factor kappa-B ρ65 (NF-κB ρ65) in hippocampal CA3 region was measured by immunohistochemistry. The results showed that [Ca(2+)] significantly increased (F = 33.218, P < 0.01) in moderate fluoride group compared with the control group, and the expression level of NF-κB ρ65 in CA3 region presented an increasing trend as fluoride concentration increased. These results indicate that increase of synaptosomes [Ca(2+)] and NF-κB ρ65 expression level may be the molecular basis of central nervous system damage caused by chronic fluoride intoxication. NF-κB ρ65 in CA3 region is probably a target molecule for fluorosis.

Percepción de ingesta de flúor a través del cepillado dental en niños colombianos / Perception of fluoride ingestion by dental brushing in Colombian children

Objetivo: describir la percepción de los padres sobre la ingesta de flúor a través del cepillado dental en los niños residentes en la ciudad de Cartagena de Indias, Colombia. Métodos: el universo del estudio lo constituyeron todos los padres residentes en la ciudad de Cartagena de Indias, con hijos en edades entre uno y cinco años. La muestra estuvo integrada por 420 individuos. Se utilizó un cuestionario estructurado, diligenciado por los participantes, con el cual se midieron tópicos relacionados con el uso de las cremas dentales a través del cepillado. Además se tuvieron en cuenta la edad, el género y el estrato socioeconómico. Los datos fueron analizados a través de pruebas de frecuencia; se asumieron intervalos de confianza al 95 por ciento. Para encontrar significación estadística se utilizó la prueba de X². Resultados: el 88,0 por ciento de los padres encuestados refiere usar el cepillado con crema dental. La edad promedio de cepillado es de 2,3 años (DE= 1,6). El 46 por ciento se cepilla dos veces al día; el tipo de crema dental más usada es la de adultos. La mayoría de los encuestados afirma que los niños han ingerido la pasta durante el cepillado. Con respecto al análisis bivariado, se encontraron diferencias entre el cepillado con crema dental y la edad (p= 0,0001), y con el estrato (p= 0,04). Además, el tipo de crema dental con la edad, (p= 0,0001) y la cantidad de pasta utilizada con la edad (p= 0,0001) y el estrato (p= 0,01). Conclusión: se perciben hábitos poco favorables, asociados al cepillado con pasta dental, los cuales pueden ser responsables de la ingestión de cantidades de flúor consideradas nocivas para la salud(AU)

Objective: To describe the parents perception on the fluoride ingestion with the use of dental brushing in the children residents in the city of Cartagena de Indias. Methods: Study universe included al parents residents in the city above mentioned whose children were aged 1-5. Sample included 420 subjects. A structural questionnaire was used headed by the participants allowing measurement of clichés related to the use of toothpastes ans brushes. Also, the gender and the socioeconomic status were took into account. Data were analyzed by frequency tests with 95 percent CI. For statistical significance we used the X2. Results: The 88 percent of parents polled refers on the use of toothpaste brushing. Mean age of brushing is of 2.3 years (SD= 1.6). The 46 percent use toothbrush twice a day, the more used toothpaste is that of adult persons. Most of polled confirms that children has ingested the toothpaste during brushing. Regarding the bivariant analysis there were differences between he brushing with toothpaste and the age (p= 0.0001) and with stratus (p= 0.04). Also, the type of toothpaste with age (p= 0.0001) and the quantity of toothpaste used according to age (p= 0.0001) and the stratum (p= 0.01). Conclusions: On note not much favourable associated with toothpaste brushing, which may account for ingestion of significant amounts of fluoride harmful for health(AU)

Activation of PERK signaling through fluoride-mediated endoplasmic reticulum stress in OS732 cells.

Our proteomical analysis of osteoblasts exposed to fluoride revealed a distinctive upregulation of proteins in osteoblast. These upregulated proteins play key roles in the protein folding. The PRK-like ER kinase (PERK) signaling, one branch of unfolded protein response (UPR) to combat ER stress, is a transcription factor needed for osteoblast proliferation and differentiation. The mechanism of skeletal fluorosis by which fluoride regulates osteoblast is not fully defined. Here we studied the effect of fluoride on PERK signaling genes and x-box binding protein 1 (xbp-1) in OS7232 cells (human osteoblast-like cell line). Meantime, genes associated with bone turnover were examined in this study. We found that early and continuous fluoride exposure increased the binding immunoglobulin protein (BiP) expression and activated the PERK signaling pathway, resulting in activation of transcription factor 4 (ATF4) and nuclear factor erythroid 2-related factor 2 (Nrf2). The altered expression of cbfa1, osteoprotegerin (OPG)/nuclear factor kappa B ligand (RANKL) were viewed in this study. These results showed fluoride impelled a distinctive ER stress response in OS732 cells, primarily by activating PERK and PERK-dependent signaling. Little effects were viewed for activating xbp-1, a common target of the other two canonical sensors of ER stress, ATF6 and IRE1. In this study the altered expression of bone turnover genes were consistent with activation of ER stress and PERK signaling. This study proved that PERK signaling play major roles in action of fluoride on osteoblast, and suggested that bone response in skeletal fluorosis may be due in part to PERK signaling pathway.

[Current trends in fluorine research]. / Aktualne kierunki badaan nad fluorem.

PURPOSE: Current topics in fluorine research are presented with emphasis on findings by researchers in Szczecin and Poland, as well as in the world. Reports are cited on the distribution of fluorine compounds in the environment, routes of penetration into living organisms, and analytical methods for the quantitative determinations of fluorine content in air, water, soil, and foods. Important contributions have been made by Polish researchers on the role and patterns of fluorides in body fluids, soft and hard tissues, which remain in direct relationship to accumulation and elimination of fluorine. So far, comprehensive studies on mutagenic effects of fluorine and its potential role in bone neoplasms, Down syndrome, and other genetic disorders have not been carried out in Poland. Worthy of mention are reports on mechanisms of action of fluorine compounds on the cellular and subcellular level. CONCLUSIONS: Finally, two achievements of recent years in the field of fluorine research are discussed briefly. The first is concerned with the use in dentistry of chemical analysis for studying mineral reconstruction of teeth throughout the lifetime of an individual. The second is in the field of medicine where molecular modeling has been applied to explain the mechanism of action of aluminofluoride complexes (AlFx) as a messenger of false information during protein biosynthesis and their apparent role in the etiology of Alzheimer's disease.

Controlling the fluoride dosage in a patient with compromised salivary function.

BACKGROUND: High-concentration topical fluorides are used commonly to with compromised salivary function due to irradiation and chemotherapy. CASE DESCRIPTION: The authors describe a 50-year-old man with previously treated cancer who was using tray-applied topical fluoride gel. He complained of gastric symptoms, difficulty in swallowing, leg muscle soreness and knee joint soreness. A computed tomographic scan revealed thickening of the esophageal walls. An upper endoscopy revealed abnormal motility. The motility test indicated high-amplitude peristalsis and hypertensive lower esophageal sphincter, and urine testing indicated high levels of systemic fluoride. The patient's fluoride regimen was altered, and within a short period his urinary fluoride levels returned to normal and his symptoms resolved. CLINICAL IMPLICATIONS: Clinicians prescribing home-applied high-concentration fluorides need to be cognizant of the symptoms of fluoride toxicity, carefully monitor the patient's compliance with the treatment regimen, and adjust the dosage or mode of application to control the total ingested dose of fluoride.

Industrial fluorosis in cattle and buffalo around Udaipur, India.

Signs of dental discolouration, difficulty in mastication, bony lesions, lameness, debility and mortality in domesticated animals, reared around superphosphate fertiliser plants located approximately 15 km north of Udaipur, Rajasthan prompted us to investigate for the occurrence of fluorosis. Out of 166 animals clinically examined, the prevalence rate was 17.4% (4/23) in calves below 1 year of age, 37.2% (16/43) in cattle between 1 and 3 years, 61.3% (46/75) in cattle above 3 years and 72% (18/25) in buffalo above 1 year. Dental fluorosis was common in buffalo compared to cattle of all the age groups. Fluoride levels in fodder and water, consumed by the animals were much higher than the recommended permissible limit. Mean fluoride concentrations in serum and urine were 1.53 +/- 1.27 and 26.4 +/- 6.17 mg l(-1) in calves below 1 year of age, 0.56 +/- 0.17 and 26.2 +/- 3.86 mg l(-1) in cattle of 1-3 years, 0.49 +/- 1.13 and 27.5 +/- 4.63 mg l(-1) in cattle above 3 years and 0.60 +/- 0.07 and 28.6 +/- 4.73 mg l(-1) in buffalo over 1 year, respectively. The values were significantly (P < 0.01) higher than those of control animals kept over a 15-km distance from the factories. Fluoride concentrations in the environmental sample collected from the affected locality were 534.4 +/- 74.9 mg kg(-1) in fodder, 1.19 +/- 0.29 mg l(-1) in pond water and 0.479 +/- 0.351 mg l(-1) in tube well water. It was concluded that the consumption of fodder and water contaminated by the fumes and dusts emitting from superphosphate fertiliser plants resulted in the development of chronic fluorotic lesions in cattle and buffalo.

[Hygienic regulation of yttrium, terbium, ytterbium and lutetium fluorides in the air of the workplace]. / K voprosu o gigienicheskoi reglamentatsii soderzhaniia ftoridov ittriia, terbiia. itterbiia i liutetsiia v vozdukhe rabochei zony.

The study (experiments on animals and on culture of rats' peritoneal macrophages) covered fluorides of rare-earth metals (REM) assigned to yttrium group--yttrium, terbium, ytterbium, lutetium. Fluorides of REM have low toxicity and cumulativity, induce no local irritation of skin and eyes. Fluorides of yttrium, terbium and lutetium, if administered into stomach, result in specific intoxication (fluorosis). Fluoride of ytterbium did not cause such intoxication. According to short-term tests of cytotoxicity, the foreseeable fibrogenic danger for ytterbium fluoride is moderate, for fluorides of yttrium, terbium and lutetium is mild. The authors recommend to control the level of yttrium, terbium and lutetium fluorides in the air of workplace through the MACs for the fluorides at 2.5 mg/cu m (maximal single concentration) and 0.5 mg/cu m (average shift concentration), the level of ytterbium fluoride as moderate fibrogenic dust at 6 mg/cu m.

Syndrome of endemic arsenism and fluorosis. A clinical study.

Sixty-five patients in Xinjiang with syndrome of endemic arsenism and fluorosis (SEAF) were investigated clinically from March 1982 to August 1989. SEAF is a kind of chronic syndrome resulting from the combined, harmful effects of two trace elements, arsenic and fluorine. Peripheral neuritis and cardiovascular changes were observed in this syndrome more often than in simple arsenism or simple fluorosis. The excessive quantities of these two trace elements in blood might have a synergic, harmful effect on the nervous and circulatory systems. No definite conclusion could be reached with regard to the morbidity of skin and visceral tumors in this series. The incidence of associated skin cancer was found to be 7.7% and an associated Grade II squamous cell carcinoma of the esophagus was encountered in one patient.

Toxicologia do flúor / Fluoride toxicology

O autor apresenta o processo toxicológico em relaçäo ao fluoreto, classificando-o e cita dados que marcam os possíveis limites de intoxicaçäo crônica e aguda, bem como refere os tipos de tratamento e cuidados para cada caso

[Morphometric study of bone in domestic pigs with fluorosis caused by coal-burning pollution].

Forty four domestic pigs were divided into 2 groups: control group: 17 pigs; fluorosis group: 27. They were fed for 14 months in the endemic area or non-endemic area respectively. In some of the pigs, double tetracycline was given for bone dynamic study, and blood and urine were collected for biochemical analyses. Iliac, tibia, fibula, the 2nd metatarsal and the 2nd vertebrae were reserved either for bone density measurement or for bone histomorphometric study. The results showed that fluoride content either in serum and in urine or in bone tissue was significantly elevated. The bone density of tibia was increased. Bone histomorphometry showed that trabecular bone volume of iliac and vertebrae was increased while that of fibula head was decreased. Trabecular resorption surface of fibula head was expanded while that of vertebrae was shrunk. As to bone dynamics, both bone formation rate and bone mineralization rate were inhibited, indicating that the toxic effects of fluoride in tremendous amount on bone remodeling. The authors suggest that the existence of osteosclerosis of axial and osteoporosis of peripheral bone in fluorosis might be related to the redistribution of calcium within the body. Furthermore, fluoride may be an osteomalacic factor for the development of osteomalacia in endemic fluorosis.

[Principles of decisional analysis applied to the screening for occupational diseases: the example of occupational fluorosis]. / Principes d'analyse décisionnelle appliqués au dépistage de maladies professionnelles: exemple de la fluorose industrielle.

In this paper, two oral presentations are combined. The first described the broad aspects of decision analysis and the second mentioned those medical data which need to be gathered in order to apply the model to industrial fluorosis. For this purpose, biological and medical observations were collected, both from workers of the aluminium industry and from controls. The five successive steps for building up a decision tree are then demonstrated, the aim of which being to evaluate the fitness of a screening strategy. A computer programme has been developed which may be applied both to occupational or non occupational diseases. Referring to industrial fluorosis, the computerized decision tree showed that screening with preshift urinary fluor, clinical and radiological signs, plus bone fluor rate is required, as soon as the risk corresponds to a 7% prevalence of the disease.