Ying J, Xu J, Shen L, Mao Z, Liang J, Lin S, Yu X, Pan R, Yan C, Li S, Bao Q, Li P. The Effect of Sodium Fluoride on Cell Apoptosis and the Mechanism of Human Lung BEAS-2B Cells In Vitro. Biological trace element research. 2017 Jan 22. doi: 10.1007/s12011-017-0937-y.
Sodium fluoride (NaF) is a source of fluoride ions used in many applications. Previous studies found that NaF suppressed the proliferation of osteoblast MC3T3 E1 cells and induced the apoptosis of chondrocytes. However, little is known about the effects of NaF on human lung BEAS-2B cells. Therefore, we investigated the mode of cell death induced by NaF and its underlying molecular mechanisms. BEAS-2B cells were treated with NaF at concentrations of 0, 0.25, 0.5, 1.0, 2.0, and 4.0 mmol/L. Cell viability decreased and apoptotic cells significantly increased as concentrations of NaF increased over specific periods of time. The IC50 of NaF was 1.9 and 0.9 mM after 24 and 48 h, respectively. The rates of apoptosis increased from 4.8 to 37.7% after NaF exposure. HE staining, electron microscopy, and single cell gel electrophoresis revealed that morphological changes of apoptosis increased with exposure concentrations. RT-PCR and Western blotting were used to detect the apoptotic pathways. The expressions of bax, caspase-3, caspase-9, p53, and the cytoplasmic CytC of the NaF groups increased, while bcl-2 and mitochondrial CytC decreased compared with that of the control group (P < 0.05). Further, the fluorescence intensities of ROS in the NaF groups were higher than those in the control group, and the membrane potential of mitochondria in the NaF group was significantly lower than that of the control group (P < 0.05). These findings suggested that NaF induced apoptosis in the BEAS-2B cells through mitochondria-mediated signal pathways. Our study provides the theoretical foundation and experimental basis for exploring the mechanisms of human lung epithelial cell damage and cytotoxicity induced by fluorine.
Ameeramja J, Perumal E. Pulmonary fluorosis: a review. Environmental science and pollution research international. 2017 Aug 25. doi: 10.1007/s11356-017-9951-z.
The increased industrialization and improvised human lifestyle lead to a surge in environmental pollution nowadays. Even the chemicals which are known as prophylactic agents were currently liable to be toxic. One among them is inorganic fluoride whose wider application in numerous processes makes it as an inevitable environmental contaminant and industrial pollutant. Although the systemic toxicity of fluoride has been extensively studied, still there is lacuna in the field of pulmonary fluoride toxicity. Hence, we have focused on the molecular mechanism of action of fluoride compounds on pulmonary system. A study of literatures that focused on the potential physiological and toxicological consequences of fluoride on pulmonary system was carried out. The goal of this review is to present an overview of the research carried out till date on the molecular aspects of fluoride exposure with emphasis on pulmonary system and their possible mechanisms.
Rocha RA, Calatayud M, Devesa V, Vélez D. Evaluation of exposure to fluoride in child population of North Argentina. Environmental science and pollution research international. 2017 Aug 8. doi: 10.1007/s11356-017-9010-9.
Fluoride is an important element for humans. It inhibits initiation and progression of dental caries and stimulates bone formation. However, excessive intake may lead to the appearance of dental and/or skeletal fluorosis and a decrease in intellectual coefficient in child populations. This study evaluates exposure to fluoride in the child population of Chaco province (Argentina) by analysis of drinking water, food and its bioaccessible fraction (quantity of fluoride solubilised by gastrointestinal digestion and available for intestinal absorption) and urine as a biomarker of internal dose. The concentration of fluoride in drinking water varied between 0.050 and 4.6 mg L-1, and 80% of the samples exceeded the WHO drinking-water guideline value (1.5 mg L-1). Fluoride concentrations in food ranged between 0.80 and 3.0 mg kg-1 fresh weight (fw), being lower in bioaccessible fraction (0.43-1.9 mg kg-1, fw). On the basis of the consumption data declared for the young child population, fluoride intake varies between 4.1 and 6.5 mg day-1, greater than the level recommended for this age group. Moreover, in some cases, concentrations of fluoride found in urine (0.62-8.9 mg L-1) exceeded those reported in areas with declared fluorosis. All data obtained show the worrying situation of child population in this area of Argentina.
Yan X, Wang L, Yang X, Qiu Y, Tian X, Lv Y, Tian F, Song G, Wang T. Fluoride induces apoptosis in H9c2 cardiomyocytes via the mitochondrial pathway. Chemosphere. 2017 Sep;182:159-165. doi: 10.1016/j.chemosphere.2017.05.002.
Numerous studies have shown that chronic excessive fluoride intake can adversely affect different organ systems. In particular, the cardiovascular system is susceptible to disruption by a high concentration of fluoride. The objectives of this study were to explore the mechanism of apoptosis by detecting the toxic effects of different concentrations of sodium fluoride (NaF) in H9c2 cells exposed for up to 96 h. NaF not only inhibited H9c2 cell proliferation but also induced apoptosis and morphological damage. With increasing NaF concentrations, early apoptosis of H9c2 cells was increased while the mitochondrial membrane potential was decreased. Compared with the control group, the mRNA levels of caspase-3, caspase-9, and cytochrome c all increased with increasing concentrations of NaF. In summary, these data suggest that apoptosis is involved in NaF-induced H9c2 cell toxicity and that activation of the mitochondrial pathway may occur.
Zhang LE, Huang D, Yang J, Wei X, Qin J, Ou S, Zhang Z, Zou Y. Probabilistic risk assessment of Chinese residents’ exposure to fluoride in improved drinking water in endemic fluorosis areas. Environmental pollution 2017 Mar;222:118-125. doi: 10.1016/j.envpol.2016.12.074.
Studies have yet to evaluate the effects of water improvement on fluoride concentrations in drinking water and the corresponding health risks to Chinese residents in endemic fluorosis areas (EFAs) at a national level. This paper summarized available data in the published literature (2008-2016) on water fluoride from the EFAs in China before and after water quality was improved. Based on these obtained data, health risk assessment of Chinese residents’ exposure to fluoride in improved drinking water was performed by means of a probabilistic approach. The uncertainties in the risk estimates were quantified using Monte Carlo simulation and sensitivity analysis. Our results showed that in general, the average fluoride levels (0.10-2.24 mg/L) in the improved drinking water in the EFAs of China were lower than the pre-intervention levels (0.30-15.24 mg/L). The highest fluoride levels were detected in North and Southwest China. The mean non-carcinogenic risks associated with consumption of the improved drinking water for Chinese residents were mostly accepted (hazard quotient < 1), but the non-carcinogenic risk of children in most of the EFAs at the 95th percentile exceeded the safe level of 1, indicating the potential non-cancer-causing health effects on this fluoride-exposed population. Sensitivity analyses indicated that fluoride concentration in drinking water, ingestion rate of water, and the exposure time in the shower were the most relevant variables in the model, therefore, efforts should focus mainly on the definition of their probability distributions for a more accurate risk assessment.
Cao J, Chen Y, Chen J, Yan H, Li M, Wang J. Fluoride exposure changed the structure and the expressions of Y chromosome related genes in testes of mice. Chemosphere. 2016 Oct;161:292-9. doi: 10.1016/j.chemosphere.2016.06.106.
It is known that during spermatogenesis, pluripotent germ cells differentiate to become efficient delivery vehicles to the oocyte of paternal DNA, and the process is easily damaged by external poison. In this study, the effects of fluoride on the body weight, fluoride content in femur, testosterone levels in serum and testis, sperm quality, and the expressions of Y chromosome microdeletion genes and protein levels were examined in testes of Kunming male mice treated with different concentrations of 0, 25, 50, 100 mg/L of NaF in drinking water for 11 weeks, respectively. The results showed that compared with the control group, fluoride contents in three treatment groups were significantly increased and the structure of testes was seriously injured. The testosterone contents and the sperm count were decreased. Sperm malformation ratio was distinctly elevated. The expressions of Sly and HSF2 mRNA were markedly reduced in 100 mg/L NaF group and Ssty2 mRNA expression was dramatically decreased in 50 and 100 mg/L NaF groups. Meanwhile, the protein levels of Ssty2 and Sly were significantly reduced in 50 and 100 mg/L NaF groups and HSF2 protein levels were significantly decreased in 100 mg/L NaF group. These studies indicated that fluoride had toxic effects on male reproductive system by reducing the testosterone and sperm count, and increasing the sperm malformation ratio, supported by the damage of testicular structure, as a consequence of depressed HSF2 level, which resulted in the down-regulation of Ssty2 and Sly mRNA and protein.
Norman M, Twetman S, Hultgren Talvilahti A, Granström E, Stecksén-Blicks C. Urinary fluoride excretion in preschool children after intake of fluoridated milk and use of fluoride-containing toothpaste. Community Dent Health. 2017 Mar;34(1):27-31. doi: 10.1922/CDH_3943Norman05.
OBJECTIVE: To assess the urinary fluoride excretion in preschool children after drinking fluoridated milk with 0.185 mg F and 0.375 mg F and to study the impact of use of fluoride toothpaste.
BASIC RESEARCH DESIGN: Double-blind cross-over study.
PARTICIPANTS: Nine healthy children, 2.5-4.5 years of age.
INTERVENTION: In a randomized order, participants drank 1.5 dl milk once daily for 7 days with no fluoride added (control), 0.185 mg fluoride added and 0.375 mg fluoride added. The experiment was performed twice with (Part I) and without (Part II) parental tooth brushing with 1,000 ppm fluoride toothpaste. The fluoride content in the piped drinking water was 0.5 mg F/L.
MAIN OUTCOME MEASURE: Urinary fluoride excretion.
RESULTS: The 24-hour urinary fluoride excretion/kg body weight varied from 0.014 mg F for the placebo intervention and non-fluoride toothpaste to 0.027 mg F for the 0.375 mg intervention with use of 1,000 ppm fluoride toothpaste. The difference compared with the placebo intervention was not statistically significant for any of the interventions when fluoride toothpaste was used (p⟩0.05) while it was statistically significantly different when non-fluoride toothpaste was used (p⟨0.05).
CONCLUSIONS: All sources of fluoride must be considered when designing community programs. With 0.5 mg F/L in the drinking water and daily use of fluoride toothpaste, most children had a fluoride intake optimal for dental health. In this setting, additional intake of fluoride milk was within safe limits up to 0.185 mg/day while conclusions about the safety of 0.375 mg/day were uncertain.