Tag Archives: toxicity

Toxic effects of fluoride on organisms

Huan Zuo, Liang Chen, Ming Kong, Lipeng Qiu, Peng Lü, Peng Wu, Yanhua Yang, Keping Chen. Toxic effects of fluoride on organisms. Life Sciences
Volume 198, 1 April 2018, Pages 18-24

Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead  to  mitochondrial  damage,  endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity.

Fluoride induced genetic alterations, skeletal fluorosis

Daiwile AP, Tarale P, Sivanesan S, Naoghare PK, Bafana A, Parmar D, Kannan K. Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis. Ecotoxicology and environmental safety. 2018 Nov 20;169:410-417. doi: 10.1016/j.ecoenv.2018.11.035.

Fluoride is an essential trace element required for proper bone and tooth development. Systemic high exposure to fluoride through environmental exposure (drinking water and food) may result in toxicity causing a disorder called fluorosis. In the present study, we investigated the alteration in DNA methylation profile with chronic exposure (30 days) to fluoride (8 mg/l) and its relevance in the development of fluorosis. Whole genome bisulfite sequencing (WGBS) was carried out in human osteosarcoma cells (HOS) exposed to fluoride. Whole genome bisulfite sequencing (WGBS) and functional annotation of differentially methylated genes indicate alterations in methylation status of genes involved in biological processes associated with bone development pathways. Combined analysis of promoter DNA hyper methylation, STRING: functional protein association networks and gene expression analysis revealed epigenetic alterations in BMP1, METAP2, MMP11 and BACH1 genes, which plays a role in the extracellular matrix disassembly, collagen catabolic/organization process, skeletal morphogenesis/development, ossification and osteoblast development. The present study shows that fluoride causes promoter DNA hypermethylation in BMP1, METAP2, MMP11 and BACH1 genes with subsequent down-regulation in their expression level (RNA level). The results implies that fluoride induced DNA hypermethylation of these genes may hamper extracellular matrix deposition, cartilage formation, angiogenesis, vascular system development and porosity of bone, thus promote skeletal fluorosis.

Fluoride toxicity to bone and soft tissue

Wei Q, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L.  A mini review of fluoride-induced apoptotic pathways. Environ Sci Pollut Res Int. 2018 Oct 18. doi: 10.1007/s11356-018-3406-z.

Fluorine or fluoride can have toxic effects on bone tissue and soft tissue at high concentrations. These negative effects include but not limited to cytotoxicity, immunotoxicity, blood toxicity, and oxidative damage. Apoptosis plays an important role in fluoride-induced toxicity of kidney, liver, spleen, thymus, bursa of Fabricius, cecal tonsil, and cultured cells. Here, apoptosis activated by high level of fluoride has been systematically reviewed, focusing on three pathways: mitochondrion-mediated, endoplasmic reticulum (ER) stress-mediated, and death receptor-mediated pathways. However, very limited reports are focused on the death receptor-mediated apoptosis pathways in the fluoride-induced apoptosis. Therefore, understanding and discovery of more pathways and molecular mechanisms of fluoride-induced apoptosis may contribute to designing measures for preventing fluoride toxicity.

Neurotoxicity of fluoride in rats

Jiang P, Li G, Zhou X, Wang C, Qiao Y, Liao D, Shi D. Chronic fluoride exposure induces neuronal apoptosis and impairs neurogenesis and synaptic plasticity: Role of GSK-3β/β-catenin pathway. Chemosphere. 2018 Sep 17;214:430-435. doi: 10.1016/j.chemosphere.2018.09.095.

Fluoride is becoming an ineluctable environmental pollutant and its longterm exposure would cause fluorosis and irreversible brain damage, but the molecular mechanisms remain far from fully understood. In the present study, we firstly evaluated the glycogen synthase kinase 3β (GSK-3β)/β-catenin pathway in the hippocampus of rats exposed to fluoride, given the well-established role of GSK-3β/β-catenin pathway in neuronal death and survival. Our data showed that sustained exposure to 50 mg/L and 100 mg/L NaF in drinking water dose-dependently induced neuronal loss and apoptosis in rat hippocampus. Neurogenesis was also weakened by fluoride administration in the hippocampal dentate gyrus region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic density 95 (PSD95) protein levels, were decreased by 100 mg/L NaF treatment, whereas 50 mg/L NaF only reduced SYP expression, indicating a compromised synaptic function. We further demonstrated that NaF, especially the higher dose, induced GSK-3β activity, with decreased inactive phosphorylated GSK-3β levels and increased GSK-3β, the active form of the kinase. Correspondingly, downstream β-catenin signaling was undermined by NaF treatment as evidenced by the fact that both two doses of NaF decreased nucleus β-catenin status and the higher dose of NaF also reduced cytoplasmic β-catenin protein expression. Taken together, the present study firstly showed the aberrant changes of GSK-3β/β-catenin signaling in the fluoride-exposed brain, highlighting the involvement of GSK-3β/β-catenin signaling in the fluoride-induced neurotoxicity.

Fluoridated water may increase dental fluorosis risk in infants

Harriehausen CX, Dosani FZ, Chiquet BT, Barratt MS, Quock RL. Fluoride Intake of Infants from Formula. J Clin Pediatr Dent. 2018 Oct 5. doi: 10.17796/1053-4625-43.1.7.

OBJECTIVE: This study aimed to assess fluoride intake in infants from formula reconstituted with water, with fluorosis risk in mind.

STUDY DESIGN: Data on water source, formula brand/type, volume of formula consumption and infant weight were collected for infants at two-, four-, six-, nine- and twelve-month pediatrician well child visits. Identified formula brands and water types were reconstituted and analyzed for fluoride concentration. Patient body mass and volume consumed/day were used to estimate fluoride intake from reconstituted formula. Descriptive statistics, one-way analysis of variance and chi-square tests were utilized.

RESULTS: All infants consumed formula reconstituted with minimally fluoridated water (0.0- 0.3 ppm). 4.4% of infants exceeded the recommended upper limit (UL) of 0.1mg/kg/day. Although mean daily fluoride consumption significantly differed among all groups, the proportion of infants at each visit milestone that exceeded daily fluoride intake of 0.1mg/kg/day was not statistically significantly different (p>0.05) for any age group. Predicted values calculated with optimally fluoridated water (0.7ppm) resulted in 36.8% of infants exceeding the UL.

CONCLUSIONS: Optimally fluoridated water may increase fluorosis risk for patients younger than six months. Future investigation should include multiple sites and multi-year follow-up to assess actual fluorosis incidence.

Toxic effects of fluoride on organisms

Zuo H, Chen L, Kong M, Qiu L, Lü P, Wu P, Chen K. Toxic effects of fluoride on organisms. Life sciences. 2018 Apr 1;198:18-24. doi: 10.1016/j.lfs.2018.02.001.

Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead to mitochondrial damage, endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity.

Fluoride toxicity alters liver enzyme activity

Perera T, Ranasinghe S, Alles N, Waduge R. Effect of fluoride on major organs with the different time of exposure in rats. Environmental health and preventive medicine. 2018 May 16;23(1):17. doi: 10.1186/s12199-018-0707-2.

BACKGROUND: High fluoride levels in drinking water in relation to the prevalence of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka were investigated using rats as an experimental model.

METHOD: The effects of fluoride after oral administration of Sodium fluoride (NaF) at levels of 0, 0.5, 5 and 20 ppm F were evaluated in adult male Wistar rats. Thirty-six rats were randomly divided into 4 groups (n = 9), namely, control, test I, II, and III. Control group was given daily 1 ml/rat of distilled water and test groups I, II, and III were treated 1 ml/rat of NaF doses of 0.5, 5, and 20 ppm, respectively, by using a stomach tube. Three rats from the control group and each experimental group were sacrificed after 15, 30, and 60 days following treatment. Serological and histopathological investigations were carried out using blood, kidney, and liver.

RESULTS: No significant differences were observed in body weight gain and relative organ weights of the liver and kidney in fluoride-treated groups compared to control group. After 60 days of fluoride administration, group I showed a mild portal inflammation with lytic necrosis while multiple areas of focal necrosis and various degrees of portal inflammation were observed in groups II and III. This was further confirmed by increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. As compared with control and other treated groups, group III showed a significantly higher serum AST activity (p < 0.05) and ALT activity (p < 0.05) after 60 days and ALP activity with a significant difference (p < 0.05) after 15, 30, and 60 days. The renal histological analysis showed normal histological features in all groups with the elevated serum creatinine levels in group III compared to those in the groups I and II (p < 0.05) after 60 days. Significantly elevated serum fluoride levels were observed in group II of 30 and 60 days and group III after 15, 30, and 60 days with respective to control groups (p < 0.05).

CONCLUSION: Taken together, these findings indicate that there can be some alterations in liver enzyme activities at early stages of fluoride intoxication followed by renal damage.