LOW/HIGH
Bittencourt LO, Dionizio A, Ferreira MKM, Aragão WAB, de Carvalho Cartágenes S, Puty B, do Socorro Ferraz Maia C, Zohoori FV, Buzalaf MAR, Lima RR. Prolonged exposure to high fluoride levels during adolescence to adulthood elicits molecular, morphological, and functional impairments in the hippocampus. Sci Rep 13(1):11083 (2023) doi: 10.1038/s41598-023-38096-8
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329641/
"At 10 mg/L of fluoride, there was increased regulation of some synaptosomal components and an opposite pattern when exposed to 50 mg/L of fluoride."
Bosakova Z, Tockstein A, Adamusova H, Coufal P, Sebkova N, Dvorakova-Hortova K - "Kinetic analysis of decreased sperm fertilizing ability by fluorides and fluoroaluminates: a tool for analyzing the effect of environmental substances on biological events" Eur Biophys J 45(1):71-9 (2016) doi: 10.1007/s00249-015-1078-x
https://link.springer.com/article/10.10 ... 015-1078-x
The acrosome reaction (AR) is the final step before sperm can penetrate the egg. At moderate fluoride exposure (A1 & A2 groups), AR was slightly reduced, but at the highest fluoride concentration (A3), there was an increase in AR.
Clark OH, Gerend PL - "Thyrotropin regulation of adenylate cyclase activity in human thyroid neoplasms" Surgery 97(5):539-46 (1985)
https://pubmed.ncbi.nlm.nih.gov/2986305/
"The effects of NaF, Gpp(NH)p, and forskolin on AC activity were additive with TSH when used at concentrations for optimal AC activity. Low concentrations of NaF and Gpp(NH)p stimulated AC activity whereas high concentrations of NaF and Gpp(NH)p assayed either together or separately inhibited AC activity."
Clark OH, Gerend PL, Nissenson RA – “Mechanisms for increased adenylate cyclase responsiveness to TSH in neoplastic human thyroid tissue” World J Surg 8(4):466-73 (1984)
"Whereas TSH and forskolin increased AC activity over the concentration range used, NaF and Gpp(NH)p had a biphasic effect; that is, they stimulated AC in a dose-dependent manner up to 30 mM NaF and 1 mM Gpp(NH)p; NaF then inhibited AC activity, and Gpp(NH)p completely eliminated AC activity in both normal and neoplastic thyroid tissue at higher concentrations."
Clark RA - "Neutrophil iodination reaction induced by fluoride: implications for degranulation and metabolic activation" Blood 57(5):913-21 (1981)
https://www.sciencedirect.com/science/a ... 7120726066
"Maximum iodination occurred after a 60-min exposure of PMN to 20–30 mM fluoride. At greater than 30 mM F–, there was a sharp decrease in iodination."
Cohen-Luria R, Sigler L, Rimon G - "Biphasic effect of sodium fluoride and guanyl nucleotides on binding to prostaglandin E2 receptors in rat epididymal adipocyte membranes" Cell Signal 1(6):561-8 (1989) doi: 10.1016/0898-6568(89)90064-8. PMID: 2561948.
https://pubmed.ncbi.nlm.nih.gov/2561948/
"Gradual increase in NaF concentrations in the presence of guanyl nucleotides resulted in stimulation of PGE2 binding at low NaF concentrations and inhibition of PGE2 binding at high NaF concentrations."
Ding X, Lai L, Jia Y, Liu X, Hu J, Chen W - "Effects of chronic fluorosis on the expression of VEGF/PI3K/AKT/eNOS in the gingival tissue of rats with orthodontic tooth movement" Exp Ther Med 27(3):121 (2024). doi: 10.3892/etm.2024.12409
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867716/
"With the extension of the application of orthodontic stress, the mRNA and protein expression levels of VEGF, PI3K, AKT and eNOS in the gingiva of the O and FO groups showed a trend of increasing at first and subsequently decreasing, which corresponds with the tooth movement cycle."
Dionizio A, Uyghurturk DA, Melo CGS, Sabino-Arias IT, Araujo TT, Ventura TMS, Perles JVCM, Zanoni JN, Den Besten P, Buzalaf MAR - "Intestinal changes associated with fluoride exposure in rats: Integrative morphological, proteomic and microbiome analyses" Chemosphere 273:129607 (2021). doi: 10.1016/j.chemosphere.2021.129607
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076095/
"The proteins with altered expression were mainly upregulated in the group treated with 10 mgF/L when compared with the control group. As for the comparison 50 mgF/L vs. control group, the proteins with altered expression were mainly downregulated in the treated group."
Duan XQ, Li YH, Zhang XY, Zhao ZT, Wang Y, Wang H, Li GS, Jing - "Mechanisms of Intracellular Calcium Homeostasis in MC3T3-E1 Cells and Bone Tissues of Sprague-Dawley Rats Exposed to Fluoride" Biol Trace Elem Res 170(2):331-9 (2016). doi: 10.1007/s12011-015-0465-6. Epub 2015 Aug 15. PMID: 26276564. Gq/11
https://pubmed.ncbi.nlm.nih.gov/26276564/
"We also found that the low dose of fluoride led to high expression levels of Cav1.2, NCS-1, and PMCA and low expression levels of IP3R and SERCA2b/ATP2A2, while the high dose of fluoride induced an increase in SERCA2b/ATP2A2 levels and decrease in Cav1.2, PMCA, NCS-1, and IP3R levels."
Farley JR, Wergedal JE, Baylink DJ - "Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone forming cells" Science 222:330–332 (1983)
Gabovich RD, Ovrutskiy GD - "Fluorine in Stomatology and Hygiene" Kazan State Medical Institute (1969)
Translated by: U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health (1977)
"While large doses inhibited thyrogenous metamorphosis of amphibian larvae, small concentrations of fluorine in a number of cases intensified it (A. Ya. Rappaport, 1945)."
Ge Y, Ning H, Gu X, Yin M, Yang X, Qi Y, Wang JD - "Thyroid function in rats on high fluoride, low iodine. Feeding effects of high fluoride and low iodine on thyroid function in offspring rats" J Integr Agric 12(3):502-8 (2013)
http://poisonfluoride.com/phpBB3/viewtopic.php?t=523
Grzegorzewska AK, Grot E, Sechman A - "Sodium Fluoride In Vitro Treatment Affects the Expression of Gonadotropin and Steroid Hormone Receptors in Chicken Embryonic Gonads" Animals (Basel) 11(4):943 (2021)
https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC8066272/
"In the testes, the lowest dose of NaF significantly decreased the expression of ...PGR. On the other hand, an increase in PGR expression was observed in the D3 group."
Guerrero-Arroyo J, Jiménez-Córdova MI, Aztatzi-Aguilar OG, Del Razo LM - "Impact of Fluoride Exposure on Rat Placenta: Foetal/Placental Morphometric Alterations and Decreased Placental Vascular Density" Biol Trace Elem Res. 2023 Oct 26. doi: 10.1007/s12011-023-03916-5
https://link.springer.com/article/10.10 ... 23-03916-5
"A statistically significant decrease in the median weight (p < 0.0001) and height (p < 0.0001) of foetuses was observed in the 2.5 mg fluoride/kg/d exposure group compared with the control, while foetuses in the 5 mg fluoride/kg/d exposure group showed a significant increase in weight (p < 0.001) and height (p < 0.0001)...Non-monotonic results were obtained in the concentration of MDA in the placental. In the 2.5 mg fluoride/kg/d group, a statistically significant increase (p < 0.0001) in the concentration of MDA was observed compared with the control group. In contrast, exposure to 5 mg fluoride/kg/d did not significantly affect (p = 0.0689) the MDA concentration in the placenta."
Gutowska I, Baranowska-Bosiacka I, Safranow K, Jakubowska K, Olszewska M, Telesiński A, Siennicka A, Droździk M, Chlubek D, Stachowska E - "Fluoride in low concentration modifies expression and activity of 15 lipoxygenase in human PBMC differentiated monocyte/macrophage" Toxicology 295(1-3):23-30 (2012)
https://www.sciencedirect.com/science/a ... 3X12000674
"Additional 15LOX-2 expression in macrophages after fluoride addition was low in 1 and 3 μM concentrations, but increased significantly after 10 μM fluoride addition..."
Hara K - "Studies on fluorosis, especially effects of fluoride on thyroid metabolism" Koku Eisei Gakkai Zasshi 30(1):42-57 (1989)
https://pubmed.ncbi.nlm.nih.gov/6936448/
https://eurekamag.com/research/006/507/006507204.php
"In groups maintained with 1 ppm F water and low fluoride diet, a somewhat high value of T3 and T4 was observed. From this, it is possible that thyroid metabolism is activated by trace amounts of fluoride. In the groups maintained with low-fluoride water (1, 5 and 10 ppm F) and high-fluoride diet, a low T3 value was observed, but no change in T4 value was seen."
Jenq SF, Jap TS, Hsieh MS, Chiang H - "The characterization of adenyl cyclase activity in FRTL-5 cell line." Chung Hua I Hsueh Tsa Chih (Taipei) 51(3):159-65 (1993)
https://pubmed.ncbi.nlm.nih.gov/8387868/
"Sodium fluoride stimulation study demonstrated dual actions of fluoride on adenylate cyclase; when the cells were assayed with increasing concentration of NaF, the AC activity increased as the concentration of NaF increased from 0.01 to 1 mM, but decreased strikingly as that concentration increased from 1 mM to 100 mM."
Jiang P, Zhang WD, Chai CY, Xiao R, Ding MX, Liu GY - "Effects of fluoride on the expression of genes related to thyroid hormone metabolism in FRTL cells" Chin J Vet Sci 29(7):885–888 (2009) PFPC Library
- TG (Thyroglobulin) mRNA: Increases at 2.5 mg/L, then sharply decreases at higher concentrations.
- TPO (Thyroid Peroxidase) mRNA: Decreases progressively and significantly starting at 2.5 mg/L.
- NIS (Sodium/Iodide Symporter) mRNA: Only starts to decrease significantly at 10 mg/L and above.
Karpova MN - "Effect of fluorine on heart arrhythmias in rats" Biull Eksp Biol Med 107(3):281-3 (1989)
https://pubmed.ncbi.nlm.nih.gov/2540850/
"The antiarrhythmic activity of fluoride was studied in a model of CaCL2-induced heart arrhythmias in male albino rats. The prolonged intake of sodium fluoride with drinking water (2 mg/l for 1 month) significantly reduced the severity of arrhythmias that was evident as an increase in the latency and a decrease in the frequency and duration of arrhythmias. A less pronounced effect was noted when the concentration of sodium fluoride was increased to 5 mg/l. At larger concentrations (11 mg/l) the fluoride exerted a toxic effect and potentiated the arrhythmogenic action of CACL2. The antiarrhythmic action of fluoride in low concentrations may be associated with the blockade of an inward Ca current."
--> Gq/11
Kienast J, Arnout J, Pfliegler G, Deckmyn H, Hoet B, Vermylen J - "Sodium fluoride mimics effects of both agonists and antagonists on intact human platelets by simultaneous modulation of phospholipase C and adenylate cyclase activity" Blood 69(3):859-66 (1987) PMID: 3028538
https://pubmed.ncbi.nlm.nih.gov/3028538/
"At lower concentrations, with a peak activity between 30 and 40 mmol/L, NaF induced aggregation and release of adenosine 5'-triphosphate (ATP) that was associated with increased formation of inositol phosphates, a rise in cytosolic free Ca2+, and phosphorylation of 20-kd and 40-kd proteins. At NaF concentrations greater than 40 mmol/L, aggregation and ATP release decreased dose-dependently in parallel with a decrease in Ca2+ mobilization, whereas neither inositol phosphate formation nor 40-kd protein phosphorylation was reduced."
Kong H, He Z, Li H, Xing D, Lin J - "The Association between Fluoride and Bone Mineral Density in US Children and Adolescents: A Pilot Study" Nutrients 16(17):2948 (2024). doi: 10.3390/nu16172948
https://www.mdpi.com/2072-6643/16/17/2948
"In the whole population, the association between water fluoride and TBHL BMD exhibited a positive correlation trend from the lowest level, 0.07 mg/L, to 0.18 mg/L, followed by a subsequent negative correlation, and ultimately reverted to a positive correlation after 0.81 mg/L."
Korkmaz R, Yüksek V, Dede S - "The Effects of Sodium Fluoride (NaF) Treatment on the PI3K/Akt Signal Pathway in NRK-52E Cells" Biol Trace Elem Res. 200(7):3294-3302 (2022) doi: 10.1007/s12011-021-02927-4
https://link.springer.com/article/10.10 ... 21-02927-4
"According to the results obtained in the study, the low NaF concentration increased the expression levels of the ERBB2, PI3K, and Akt genes, while the higher concentrations did not significantly affect these levels. The expression of mTOR decreased at all given concentrations. The expression of the TP53 gene did not change at the low concentration, while it increased at the high concentrations."
Koskela A, Finnilä MA, Korkalainen M, Spulber S, Koponen J, Håkansson H, Tuukkanen J, Viluksela M - "Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation" Toxicol Appl Pharmacol 301:14-21 (2016)
https://pubmed.ncbi.nlm.nih.gov/27068293/
"In osteoblasts, low concentrations of PFOA increased osteocalcin (OCN) expression and calcium secretion, but at PFOA concentrations of 100μM and above osteocalcin (OCN) expression and calcium secretion were decreased. The number of osteoclasts was increased at all PFOA concentrations tested and resorption activity dose-dependently increased from 0.1-1.0μM, but decreased at higher concentrations. The results show that PFOA accumulates in bone and is present in bones until the old age. PFOA has the potential to influence bone turnover over a long period of time. Therefore bone is a target tissue for PFOA, and altered bone geometry and mineral density seem to persist throughout the life of the animal."
Ladics GS, Stadler JC, Makovec GT, Everds NE, Buck RC -"Subchronic toxicity of a fluoroalkylethanol mixture in rats" Drug Chem Toxicol 28(2):135-58 (2005)
https://pubmed.ncbi.nlm.nih.gov/15865257/
"Interestingly, more fluorosis-type lesions were produced after longterm administration of low doses of fluoride than after short-term administration of high doses (Angmar-Mansson and Whitford, 1984; Nelson et al., 1989)."
Lau KH, Baylink DJ - "Molecular mechanism of action of fluoride on bone cells" JBone Miner Res 13(11):1660-7 (1998)
https://asbmr.onlinelibrary.wiley.com/d ... 13.11.1660
Li Fucheng - "Studies on the chronic dose-effects of fluoride on element contents and biochemical indices in serum of rats of young age groups" Studies of Trace Elements & Health (3) (1999)
http://en.cnki.com.cn/Article_en/CJFDTo ... 903003.htm
Li Junjun, Zhao Qiaoyu, Li Yue, Bao Ying, Li Bingyang, Yan Huazhu, Huo Si Meng, Fan Yumei, Yang Yanmei, Gao Yanhui - "Effects of embryonic fluoride exposure on skeletal development in zebrafish" Chinese Journal of Endemic Diseases 37(1):24-29 (2018). DOI: 10.3760/cma.j.issn.2095-4255.2018.01.006
"Low-dose fluoride exposure made zebrafish embryos bone sclerotic, and high-dose fluoride exposure made zebrafish embryos osteoporotic."
Liu HL, Cheng XM, Fan QTQ - "Water fluoride concentration and human health effects" Chinese J Endemiology 12(1):21–23 (1993)
"...when the fluoride concentration in drinking water reaches 0.58mg/l - 1.59 mg/l, ALP activity is increased, while it decreases slowly when water fluoride concentration is between 1.60 mg/l and 3.37 mg/l."
Ma J, Song Y, Liu K - "Study of the expression level of zinc finger factor osterix associated with fluoride bone injury" Journal of Hygiene Research. 39(6):682-4 (2010) Chinese
https://pubmed.ncbi.nlm.nih.gov/21351630/
"The levels of Osx protein in F exposure groups increased at first and then decreased with the levels of F exposure."
Ma R, Liu S, Qiao T, Li D, Zhang R, Guo X - "Fluoride Inhibits Longitudinal Bone Growth by Acting Directly at the Growth Plate in Cultured Neonatal Rat Metatarsal Bones" Biol Trace Elem Res (2019) doi: 10.1007/s12011-019-01997-9
"Linear measurements demonstrated that fluoride induced a biphasic effect on longitudinal bone growth in organ culture, with a significant growth inhibition at a high concentration (10-4 M) and a stimulatory action at low concentration (10-6 M) of fluoride."
Ma Y, Liu Y, Liu X, Li M, Cui J, Guan Z, Pei J, Gao Y - "Fluoride exposure and prevalence of osteochondroma in drinking water Endemic fluorosis areas of Heilongjiang Province, China: a cross-sectional study" Int J Environ Health Res Nov 3:1-14 (2023). doi: 10.1080/09603123.2023.2277336. Epub ahead of print
https://www.tandfonline.com/doi/abs/10. ... 23.2277336
"Logistic regression analysis found that compared to 1st quartile participants, the prevalence of OC was 73% lower in the 2nd quartile participants of WF (Water fluoride), and 3.4 times higher among the 2nd quartile UF (Urinary fluoride) participants. Our study suggests that 0.259-0.420 mg/L of WF may be considered an appropriate level for reducing OC prevalence, while UF (≥0.750 mg/L) could slightly increase the prevalence of OC."
Martin JJ, Schatz A - "Some peculiar non-linear relationships between the concentration of fluoride and its biological activity" - Proceedings of the Pennsylvania Academy of Science 35:187-190 (1961)
https://www.jstor.org/stable/44110224
Misra UK, Gawdi G, Pizzo SV - "Beryllium fluoride-induced cell proliferation: a process requiring P21(ras)-dependent activated signal transduction and NF-kappaB-dependent gene regulation" J Leukoc Biol 71(3):487-94 (2000)
https://pubmed.ncbi.nlm.nih.gov/11867686/
https://jlb.onlinelibrary.wiley.com/doi ... b.71.3.487
"At low concentration (1-5 nM), BeF(2) caused an approximate twofold increase in [(3)H]thymidine uptake and cell number, but above 5 nM, it showed cytotoxic effects. ...We conclude that BeF(2) at low concentration exerts its mitogenic effects in peritoneal macrophages by elevating [Ca(2)(+)](i), which triggers the activation of p21(ras)-dependent MAPK signaling cascades."
--> G/q 11
Naka T, Maruyama S, Nagao T, Takayama F, Maki J, Yasui T, Sakagami H, Ohkawa S - "Inhibition of branching morphogenesis of mouse fetal submandibular gland by sodium fluoride--protection by epidermal growth factor" In Vivo 19(2):327-34 (2005)
https://pubmed.ncbi.nlm.nih.gov/15796194/
"At a lower concentration of NaF (< 2 microM), the branching morphogenesis was slightly enhanced, whereas at a higher concentration of NaF (4 - 8 microM), it was almost completely inhibited. ...The number of buds was slightly increased at lower concentrations of NaF (1 uM), but decreased at higher concentrations (>2 uM)...The inhibitory effect of NaF became apparent above 4 uM (Figure 1)."
Refsnes M, Skuland T, Låg M, Schwarze PE, Øvrevik J - "Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8) induction in lung epithelial cells" J Inflamm Res 7:169-85 (2014)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270361/
Scheinin A, Kalijarvi E, Harjola O, Heikkinen K - "Prevalence of dental caries and dental health in relation to variable concentration of fluorides in drinking water" Acta Odontol Scand 22:229-254 (1964) [SEE: Kunzel, 1976]
https://medicaljournalssweden.se/actaod ... 6307/41431
"The results regarding the number of erupted teeth and the number of retained deciduous teeth suggest that the eruption rate of the permanent teeth is slightly delayed at high fluoride concentrations. On the other hand, the results also suggest that the eruption of the permanent teeth might be slightly accelerated at a moderate level (0.40-0.99 mg/l) of water fluoride"
“Similarly NaF stimulated glucose production in hepatocytes from fasted rats. The maximal stimulation was observed with about 0.15-0.25 mM NaF. At NaF concentrations greater than 1.5 mM a decrease in glucose production was observed. It is concluded that NaF increases the level of cAMP and alters glucose metabolism in intact hepatocytes.”
Shahed AR, Miller A, Chalker D, Allmann DW - "Effect of sodium fluoride on cyclic AMP production in rat hepatocytes" J Cyclic Nucleotide Res. 5(1):43-53 (1979)
https://pubmed.ncbi.nlm.nih.gov/220288/
"When hepatocytes from fed rats were incubated with 0.05-5 mM NaF there was an increase in amount of glucose released from endogenous sources. Also NaF resulted in a decrease in lactate and pyruvate production. Similarly NaF stimulated glucose production in hepatocytes from fasted rats. The maximal stimulation was observed with about 0.15-0.25 mM NaF. At NaF concentrations greater than 1.5 mM a decrease in glucose production was observed. It is concluded that NaF increases the level of cAMP and alters glucose metabolism in intact hepatocytes."
Shi G, Cui Q, Zhang H, Cui R, Guo Y, Dai J - "Accumulation, Biotransformation, and Endocrine Disruption Effects of Fluorotelomer Surfactant Mixtures on Zebrafish" Chem Res Toxicol (2019) 32(7):1432-1440
https://pubmed.ncbi.nlm.nih.gov/31251046/
(T3 and T4 levels decreased in the 50 and 500 μg/L females and increased T4 level in 500 μg/L exposed males.)
Smith MC - "Effects of Fluorine Upon Rate of Eruption of Rat Incisors, and its Correlation with Bone Development and Body Growth" JDR 14(2):139-144 (1934)
https://journals.sagepub.com/doi/abs/10 ... lCode=jdrb
"When the ration included 0.05 percent of NaF, lower incisors erupted at about 87 percent of the rate recorded for controls; inclusion of 0.1 percent resulted in an eruption rate only 52.9 percent of normal."
Song YE, Tan H, Liu KJ, Zhang YZ, Liu Y, Lu CR, Yu DL, Tu J, Cui CY - "Effect of fluoride exposure on bone metabolism indicators ALP, BALP, and BGP" Environ Health Prev Med 16(3):158-63 (2011)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078298/
"From these results, we know that a low fluoride dose combined with a short exposure time increased serum ALP activity; however a high fluoride dose combined with a short exposure time resulted in an inhibition of serum ALP activity."
Susheela AK, Sharma YD - "Chemical profile of blood in fluoride toxicity III. Plasma fibrinogen levels In rabbit" Toxi Exp 105-109 (1980)
https://fluorideandfluorosis.com/Reprin ... 9,1980.pdf
(Bi-phasic)
Taylor ML, Maconnachie E, Frank K, Boyde A, Jones SJ - "The effect of fluoride on the resorption of dentine by osteoclasts in vitro" J Bone
Miner Res 5(Suppl 1):121-130 (1990)
https://asbmr.onlinelibrary.wiley.com/d ... 5650051391
"A complex interplay of stimulation of some cells in the culture with indirect stimulation of osteoclasts and direct inhibition of osteoclastic resorptive function may be operating at this concentration of fluoride."
Thaweboon S, Thaweboon B, Chunhabundit P, Suppukpatana P - "Effect of fluoride on human dental pulp cells in vitro" Southeast Asian J Trop Med Public Health 34(4):915-8 (2003) PMID: 15115110
https://pubmed.ncbi.nlm.nih.gov/15115110/
"It was found that fluoride at 5 ppm concentration significantly stimulated cell proliferation and ALP activity between 24 and 48 hours after exposure whereas at higher concentrations (40 - 80 ppm), fluoride significantly inhibited cell growth and ALP activity after 48 hours (Student's t test)."
Wang X, Li J, Fan Y, Zhang X, Yang Y, Gao Y - "Zebrafish larvae as a model for investigating dual effects of fluoride on bone development" Toxicol Appl Pharmacol 117357 (2025) doi: 10.1016/j.taap.2025.117357
https://www.sciencedirect.com/science/a ... 8X25001334
"In conclusion, different fluoride doses cause osteoporosis and osteosclerosis in zebrafish larvae, linked to enhanced osteogenic and osteoclastic activities and abnormal key bone - forming protein expression."
Wang G, Wang T, Zhang X, Chen J, Feng C, Yun S, Cheng Y, Cheng F, Cao J - "Sex-specific effects of fluoride and lead exposures on histology, antioxidant physiology, and immune system in the liver of zebrafish (Danio rerio)" Ecotoxicology 31(3):396-414 (2022)
https://pubmed.ncbi.nlm.nih.gov/35088223/
"Moreover, F and Pb exposure of male zebrafish increased pro-inflammatory and anti-inflammatory cytokines expression, which was decreased after 90 days of exposure....F and Pb showed synergistic or additive effects. Male zebrafish were found to be more sensitive to F and Pb than female zebrafish."
Wang J, Li G, Li Y, Zhao Y, Manthari RK, Wang J - "The Effects of Fluoride on the Gap-Junctional Intercellular Communication of Rats' Osteoblast" Biol Trace Elem Res 193(1):195-203 (2020). doi: 10.1007/s12011-019-01692-9
https://link.springer.com/article/10.10 ... 19-01692-9
"The scrape loading and dye transfer experiment showed that the GJIC were increased in the 0.01 mM NaF group and decreased in the 0.5 and 1 mM NaF groups. In addition, the mRNA expressions of Cx43, Cx45, and OCN, and the protein expressions of Cx43 were increased in the 0.01 mM NaF group and decreased in the 0.5 and 1 mM NaF groups."
Wang X, Zheng R, Yao Q, Liang Z, Wu M, Wang H - "Effects of fluoride on the histology, lipid metabolism, and bile acid secretion in liver of Bufo gargarizans larvae" Environ Pollut 254(Pt B):113052 (2019). doi: 10.1016/j.envpol.2019.113052
https://www.sciencedirect.com/science/a ... 9119317749
"The expression of PPARa was significantly lower in 50 mg/L of NaF group, but was significantly higher in 10 mg/L of NaF group (p < 0.01)."
Wei Y, Zeng B, Zhang H, Chen C, Wu Y, Wang N, Wu Y, Shen L - "iTRAQ-Based Proteomics Analysis of Serum Proteins in Wistar Rats Treated with Sodium Fluoride: Insight into the Potential Mechanism and Candidate Biomarkers of Fluorosis" Int J Mol Sci 17(10):1644 (2016)
https://pubmed.ncbi.nlm.nih.gov/27690006/
"Taken together with the expression pattern of the total proteins, this implies that low-dose NaF may promote complement, inflammation, and immune responses, whereas moderate- and high-dose NaF may inhibit these responses."
Wu Yanli, Xiang Rong, Xu Xiaodong, Cao Fajun, Fan Xiang, Wei Yan - "Expression of G protein in bone tissue of rats with chronic fluoride poisoning" Journal of Environment and Health (4) (2014)
https://www.alljournals.cn/view_abstrac ... ADE6B277ED
"With the increase of NaF exposure dose, the fluoride content in the urine and bones of rats showed an upward trend; while the Gs and Gi contents in the bone tissue showed a trend of increasing first and then decreasing."
Yan Q, Zhang Y, Li W, Denbesten PK - "Micromolar fluoride alters ameloblast lineage cells in vitro" J Dent Res 86(4):336-40 (2007)
"Fluoride had a biphasic effect on cell proliferation, with enhanced proliferation at 16 microM, and reduced proliferation at greater than 1 mM F."
Yu H, Jiang N, Yu X, Zhao Z, Zhang X, Xu H - "The role of TGFβ receptor 1-smad3 signaling in regulating the osteoclastic mode affected by fluoride" Toxicology 393:73-82 (2018)
https://pubmed.ncbi.nlm.nih.gov/29127033/
"Results demonstrated that different doses of fluoride exhibited a biphasic effect on osteoclast cell viability, differentiation, formation and function. It indicated that a low dose of fluoride treatment stimulated them, but high dose inhibited them."
Yuan SD, Liu GS, Sun GY, Qu WJ - "Thyroid nucleic acid levels in acute and chronic fluorosis" Fluoride 24(1):12-16 (1991)
Xiang Q, Zhou M, Wu M, Zhou X, Lin L, Huan J, Liang Y - "Relationships between daily total fluoride intake and dental fluorosis and dental caries" J Nanjing Med Univ 1:33-39 (2009) PFPC Library- Rabbits
Low dose (NaF 5 mg/kg/day; ≈2.3 mg F⁻/kg/day):
Females: thyroid RNA increased significantly (P < 0.001).
Males: no significant change.
Higher doses (10–50 mg/kg/day):
Both sexes: thyroid RNA and DNA decreased sharply, with losses up to ~60–65%.
http://218.28.6.71:81/Qikan/Article/Detail?id=29194046
"There was also a significant negative (inverse) dose-response relationship between the daily total intake of fluoride and the overall prevalence of dental caries, the prevalence of which decreased when the daily total intake of fluoride increased up to 3.32 mg/child/day. However, at higher levels of daily total intake of fluoride the prevalence of dental caries increased, giving rise to a U-shaped dose-response relationship curve."
Xu H, Zhou YL, Zhang JM, Liu H, Jing L, Li GS - "Effects of fluoride on the intracellular free Ca2+ and Ca2+-ATPase of kidney" Biol Trace Elem Res 116(3):279-88 (2007)
https://pubmed.ncbi.nlm.nih.gov/17709908/
"To sum up, the effect of fluoride on Ca2+-ATPase is a similar to a dose-effect relationship phenomenon characterized by low-dose stimulation and high-dose inhibition, and the increase of [Ca2+]i probably plays a key role on the mechanism of renal injury in fluorosis."
--> Gq/11
Xu Gang, Wang Jinming, Ma Shuhui, Zhan Yaqi, Ma Haili - "Effects of fluoride on the expression of ERK pathway-related genes and proteins in mouse spleen lymphocytes" Journal of Animal Science and Veterinary Medicine 11:1888–1894 (2014)
http://218.28.6.71:81/Qikan/Article/Det ... 4949485049
"The results showed that the activation of the ERK pathway in mouse splenic lymphocytes could be inhibited by low-concentration fluoride, but with the increase of fluoride concentration, the inhibition trend gradually decreased and turned to promotion."
Zhang W, Chai C, Zhang Y - "Expressions of iNOS and VEGF mRNAs in thyroid gland of rat with goiter induced by fluoride" J Chinese Veterinary Science 38(3) (2008) (In Chinese)
http://poisonfluoride.com/phpBB3/viewtopic.php?p=976
--> Gq/11 (150 days)
Zhang Y, Zhou BH, Tan PP, Chen Y, Miao CY, Wang HW - " Key Role of Pro-inflammatory Cytokines in the Toxic Effect of Fluoride on Hepa1-6 Cells" Biol Trace Elem Res 197(1):115-122 (2020)
https://pubmed.ncbi.nlm.nih.gov/31983054/
"The content of IL-6 remarkably increased with increasing fluoride concentrations up to 2 mmol/L, and then markedly decreased at 3, 4, and 5 mmol/L fluoride; the decreasing trend of IL-6 content under high fluoride exposure is consistent with the decrease in Hepa1-6 cell viability observed at the same concentration."
Zhao H, Chai L, Wang H - "Effects of fluoride on metamorphosis, thyroid and skeletal development in Bufo gargarizans tadpoles" Ecotoxicology 22(7):1123-32 (2013)
doi: 10.1007/s10646-013-1099-0. Epub 2013 Aug 10. PMID: 23934448.
https://pubmed.ncbi.nlm.nih.gov/23934448/
"Fluoride at 5 mg L(-1) can stimulate bone mineralization, while fluoride at 50 mg L(-1) can retard deposition of calcium."
Zhao L, Su J, Liu S, Li Y, Xi T, Ruan J, Liang KX, Huang R - "MAP kinase phosphatase MKP-1 regulates p-ERK1/2 signaling pathway with fluoride treatment" Biochem Biophys Res Commun 542:65-72 (2021) doi: 10.1016/j.bbrc.2020.12.100. Epub ahead of print. PMID: 33493990.
https://pubmed.ncbi.nlm.nih.gov/33493990/
"Using this system, we demonstrated that fluoride exposure led to an inhibition of p-MEK and p-ERK1/2 with a subsequent increase in MKP-1 expression in a dose-dependent manner. We further identified, under high dose fluoride, MKP-1 acted as a negative regulator of the fluoride-induced p-ERK1/2 signaling, leading to downregulation of CREB, c-myc, and Elk-1. Our results identify a novel MKP-1/ERK signaling mechanism that regulates dental fluorosis and provide a framework for studying the molecular mechanisms of intervention and fluorosis remodeling under normal and pathological conditions. MKP-1 inhibitors may prove to be a benefit therapeutic strategy for dental fluorosis treatment."
Zhao W, Guénard H - "The inhibitory effect of fluoride on carbachol-induced bovine bronchial contraction" Respir Physiol 108(2):171-9 (1997)
https://pubmed.ncbi.nlm.nih.gov/9232690/
Zhao ZT, Shi LQ, Lv P, Xu H, Li GS - "Level of reduced glutathione and oxidized glutathione in a mouse bone cell line MC3T3-E1 cells exposed to fluoride" Chin J Endemiol 31(5):511–514 (2012)
A low dose of fluoride (2.0 mg/L F−) could stimulate the viability of mouse osteoblastic cell line MC3T3-E1 but high doses of fluoride (8.0 and 12.0 mg/L F−) significantly inhibited the viability.
Sepracor Patent:
Aberg G, Jerussi TP, Mccullough JR - "Nsaid/fluoride periodontal compositions" WO1997039729A1
https://patents.google.com/patent/WO1997039729A1
"Fluoride alone at the 26 mM concentration (0.05%) caused a 108% stimulation of PGE2 production, whereas inhibition of 12 and 92% were respectively observed at 52 mM and 260 mM."
SHORT/LONG
Araujo TT, Barbosa Silva Pereira HA, Dionizio A, Sanchez CDC, de Souza Carvalho T, da Silva Fernandes M, Rabelo Buzalaf MA - "Changes in energy metabolism induced by fluoride: Insights from inside the mitochondria" Chemosphere 236:124357 (2019). doi: 10.1016/j.chemosphere.2019.124357
https://www.sciencedirect.com/science/a ... via%3Dihub
"The dose of 15 mgF/L, when administered for 20 days, reduced glycolysis, which was counterbalanced by an increase in other energetic pathways. At 60 days, however, an increase in all energy pathways was observed. On the other hand, the dose of 50 mgF/L, when administered for 20 days, reduced the enzymes involved in all energetic pathways, indicating a lower rate of energy production, with less generation of ROS and consequent reduction of antioxidant enzymes. However, when the 50 mgF/L dose was administered for 60 days, an increase in energy metabolism was seen but in general no changes were observed in the antioxidant enzymes.
Arslan S, Keleş İ - "The relationship between the levels of the fluoride ion and the thyroid hormones in goats with fluorosis" Fluoride 50(1 Pt 2)135–142 (2017)
https://www.fluorideresearch.org/501Pt2 ... 42_sfs.pdf
"No clear reason was found for the finding, in the present study, that the FT3 was significantly increased in the 1–3-years-old goats with fluorosis compared to the 1–3-years-old control goats (p<0.05)..... Significant decreases were present in the levels of TT3 (p<0.01) and FT4 (p<0.001) in the older goats with fluorosis, 3–5-years-old and >5-years-old, compared to the younger animals, aged 1–<3 years."
Bo X, Mu D, Wu M, Xiao H, Wang H - "The morphological changes and molecular biomarker responses in the liver of fluoride-exposed Bufo gargarizans larvae" Ecotoxicol Environ Saf 151:199-205 (2018). doi: 10.1016/j.ecoenv.2018.01.027
https://linkinghub.elsevier.com/retriev ... 18)30037-X
"Similarly, in comparison to nonexposed controls, the transcript levels of SCP and PPARα significantly decreased at 42.4 mg F-/L for 24h, 48h. In contrast, the transcript levels of PPARα and ACOX significantly increased in tadpoles treated with 42.4 mg F-/L for 72h."
Chaneles J - "Action de l'iode sur la fluorose chronique" Compt. Rend 102:863 (1929) Translated from French . Public Health Service, Air Pollution Technical Information Center, 2p ., Sept. 15, 1969.
"The growth of rats receiving fluorine was better than that of the control group for 3 months, then slackened, and on the sixth month was less."
Ge Y, Ning H, Gu X, Yin M, Yang X, Qi Y, Wang JD - "Thyroid function in rats on high fluoride, low iodine. Feeding effects of high fluoride and low iodine on thyroid function in offspring rats" J Integr Agric 12(3):502-8 (2013)
http://poisonfluoride.com/phpBB3/viewtopic.php?t=523
"Decrease in TT3 at 20- and 90-days and increase in TT3 at 30- and 60-days were found in HiF+LI group....The levels of TSH in serum rocketed at day 20, and then dropped in the next stages in experimental groups."
Guo Wenjing, Wang T, Xue W, et al. - "Interference effects of fluoride on thyroid endocrine function in Zebrafish" Acta Scientiae Circumstantiae 39(4):1340-1347 (2019)
https://www.actasc.cn/hjkxxb/ch/reader/ ... 001&flag=1
https://global.cnki.net/kcms/detail/det ... X201904037
"The levels of T3 and T4 had an increasing trend after exposure for 45 days, while the T4 level had a decreasing trend and was significantly reduced in 80 mg·L-1 fluoride group after exposure for 90 days (p<0.05)".
Guo XW, Lu CH, Bian JC - "Effects of fluoride and selenium on thyroid tissues and function in rats" Studies of Trace Elements and Health (4) (1998)
viewtopic.php?p=904
"The results showed that the proliferation of thyroid follicular epithelial cells was active early, and the level of free thyroid hormone was significantly increased. In the later stage, thyroid follicular epithelial cells showed degenerative changes, and the levels of FT3 and T4 were significantly reduced...It suggested that F could excite thyroid gland to make thyroid functions in state of high compensation at early stage, and yet it could inhibit thyroid gland to cause hypothyroidism at the later stage."
Guo X, Shan Z, Teng W - "Experimental Study on Effects of Excessive Fluoride and Iodine Fluoride on Thyroid Function and Morphology" Chinese Journal of Internal Medicine 10:846-847 (2006)
http://222.198.130.40:81/Qikan/Article/ ... d=23033495
Guo X, Lu C, Bian J - "Effects of fluoride and selenium on thyroid tissues and function in rats" Studies of Trace Elements and Health 15(4):9-10,53 (1998)
Hu Aiwu, Liu Xiaoyang, Qin Yide - "Effect of fluorine on triiodothyronine and thyroxin in mice" Journal of Bengbu Medical College (4)(2008)
https://en.cnki.com.cn/Article_en/CJFDT ... 804004.htm
viewtopic.php?f=80&t=4769
"Fluorine at a high dose might interfere the secretive function of thyroid gland in mice. It enhances the secretion of the thyroid gland in the short-term but inhibits the secretive function in long term. The changes of the secretive function of thyroid gland are correlative with the dose of fluorine and the time length of test."
Jiang Y, Guo X, Sun Q, Shan ZY, Teng W - "Effects of excess fluoride and iodine on thyroid function and morphology" Biological Trace Element Research 170(2):382–389 (2016)
https://link.springer.com/article/10.10 ... 015-0479-0
viewtopic.php?f=7&t=1778
Kolisnyk I, Voloshin O, Savchenko I, Yanchevskyi O, Rashidi B - "Enzymatic activity in microsomes, lipid peroxidation of mice hepatocytes under the sodium fluoride" Georgian Med News (310):169-176 (2021)
https://pubmed.ncbi.nlm.nih.gov/33658427
"Increase in the activity of NAD (P) H-cytochrome c reductase in the microsomal fraction of the liver at the beginning of the study and a gradual decrease on the 50th and 60th days when using both dosages. The same dynamics was observed for NADH-cytochrome c reductase...Indicators of cytochrome P-450 cytochrome b5 were increased up to 30 days and gradually decreased by 60 days."
Kuang P, Cui H, Yu L - "Sodium fluoride suppresses spleen development through MAPK/ERK signaling pathway in mice" Ecotoxicol Environ Saf 241:113764 (2022) doi: 10.1016/j.ecoenv.2022.113764
https://www.sciencedirect.com/science/a ... 1322006042
"Additionally, the mRNA and protein levels of MEK1/2 were increased on the 21st day of the experiment, while reduced on the 42nd day."
Liu Hongliang, Yu Linyu, Cui Yushan, Zeng Qiang, Zhao Liang, Hou Changchun, Wang Aiguo - "Influence of Long Term Excessive Fluoride Intake on the Morphology and Function of Thyroid in Rats" Journal of Environmental Hygiene 3(5): 390-393, 397 (2013)
http://html.rhhz.net/hjwsxzz/html/52248.htm
viewtopic.php?f=21&t=1815
"Serum TT 4 and FT 4 levels of all fluoride exposure groups increased significantly after 2 months (P less than 0.05), and then began to decrease."
Liu X, Li Z, Lia Y, Ding X - "Effect of Chronic Fluorosis Environment on Expression of VEGF and eNOS in Periodontal Tissue During Orthodontic Tooth Movement in Rats" Journal of Oral Science Research 8:727-734 (2024) PFPC Library
http://218.28.6.71:81/Qikan/Article/Det ... 7112765417
NOTE: Gq/11 "The expression of VEGF and eNOS proteins in the O and FO groups showed an increasing trend followed by a decreasing trend over time,with a peak on the third day. Conclusion: Chronic fluorosis can inhibit the expression of VEGF and eNOS in the periodontal tissue of rats during tooth movement."
Liu GY, Chai CY, Kang SL - "Effects of fluoride on the activity of deiodinase in the liver of chickens" Chin J Vet Med 39:14-5 (2003)
http://www.cqvip.com/qk/92143x/200305/7939505.html
(First increase in D1, then decrease)
First, fluoride causes an increase in D1, then, after 90 days, a severe decrease. Downregulation of D1 leads to an increase in circulating rT3, because the conversion of rT3 to T2 is significantly reduced, resulting in an accumulation of rT3. (Compare to Zhao et al., 1998;1992)
Lu CH, Guo XW, Bian JC, Ye P, Xian S, Liu Y, Ji QX - "Experimental Study on the Effect of High Fluoride and Selenium Supplementation on Rat Thyroid" Chinese Journal of Endemic Diseases" (2):105-107 (1998)
http://yuxiqbs.cqvip.com/Qikan/Article/ ... arch_Index
"The thyroid follicular epithelium proliferated actively and free thyroid hormone increased in the early stage; the thyroid follicular epithelium degenerated in the later stage, and the levels of FT3 and T4 decreased. This suggests that high fluoride excites the thyroid gland in the early stage, and the thyroid function is highly compensated, and the thyroid function is suppressed in the later stage, resulting in hypothyroidism; the changes of fluoride and thyroid tissue and function are closely related to the time of fluoride intake."
Ma J, Song Y, Liu K - "Study of the expression level of zinc finger factor osterix associated with fluoride bone injury" Journal of Hygiene Research. 39(6):682-4 (2010) Chinese
https://pubmed.ncbi.nlm.nih.gov/21351630/
"The levels of Osx protein in F exposure groups increased at first and then decreased with the levels of F exposure...In comparison with the 0 h F exposure group, the trend of Osx was the same, the results of RT-PCR indicated that the levels of Osx mRNA significantly increased in the group of 24-48 h F exposure groups (P < 0.05), overall, the trends of Osx mRNA level were similar to the trend of Osx protein, which went up at first and then went down in each group."
Nagendra AH, Najar MA, Bose B, Shenoy PS - "High concentration of sodium fluoride in drinking water induce hypertrophy versus atrophy in mouse skeletal muscle via modulation of sarcomeric proteins" J Hazard Mater 432:128654 (2022). doi: 10.1016/j.jhazmat.2022
https://www.sciencedirect.com/science/a ... via%3Dihub
"Results indicated an increase in the muscle mass (hypertrophy) in vivo and myotubes ex vivo by activating the IGF1/PI3/Akt/mTOR signalling pathway due to short term NaF exposure. The long-term exposure of mice to NaF caused loss of muscle proteins leading to muscle atrophy due to activation of the ubiquitin-proteasome pathway."
Pereira HABS, Araújo TT, Dionizio A, Trevizol JS, Pereira FS, Iano FG, Faria Ximenes V, Buzalaf MAR - "Increase of complex I and reduction of complex II mitochondrial activity are possible adaptive effects provoked by fluoride exposure" Helyion 7(1): e06028 (2021)
https://www.cell.com/action/showPdf?pii ... %2900133-X
"The mitochondrial complex I-III was significantly activated in the groups treated with 50 mgF/L for 20 days and 15 mgF/L for 60 days. The complex II-III was significantly reduced in the group treated with the higher F dose for 60 days."
Sarri E, Claro E - "Fluoride-induced depletion of polyphosphoinositides in rat brain cortical slices: a rationale for the inhibitory effects on phospholipase C" Int J Dev Neurosci 17(4):357-67 (1999) doi: 10.1016/s0736-5748(99)00034-9
https://onlinelibrary.wiley.com/doi/abs ... %2900034-9
"The inhibitory effects of fluoride on the release of 3H-inositol phosphates in slices were not apparent in a pulse [3H]inositol-labeling strategy, but became dramatic in a continuous labeling protocol, particularly at long incubation times."
Susheela AK, Sharma YD - "Chemical profile of blood in fluoride toxicity III. Plasma fibrinogen levels In rabbit" Toxi Exp 105-109 (1980)
https://fluorideandfluorosis.com/Reprin ... 9,1980.pdf
(Bi-phasic)
Wang Nanlan, Ao Quan, Lei Lu, Zeng Beibei, Wu Yanqiu, Zhang Hua, Wei Yan - "Effects of sodium fluoride on proliferation activity, alkaline phosphatase activity and osteocalcin mRNA expression in rat osteosarcoma cells" Journal of Environment and Health (9):773-776 (2016)
https://www.alljournals.cn/view_abstrac ... 6F01DE79C5
"With the increase of NaF concentration, the ALP activity in the culture fluid and cells of UMR-106 cells showed an upward trend; with the extension of NaF exposure time, the ALP activity in the cell culture fluid showed an upward trend, while the ALP activity in the cells showed a trend of first increasing and then decreasing."
Wu Yanqiu, Chen Xuanhao, Dai Yougang, Wang Nanlan, Wei Yan - "Effects of sodium fluoride on osteogenic activity markers of rat osteosarcoma cells UMR-106" Modern Preventive Medicine (5) (2018)
https://www.alljournals.cn/view_abstrac ... D73C8E13BC
"Sodium fluoride has a bidirectional effect on the osteogenic activity of osteosarcoma UMR-106 cells."
Yang Xiaodong, Chen Anyu - "The effect of fluoride on the proliferation of rat osteoblast-like cells" West China Journal of Stomatology (3) (1993)
http://www.cnki.com.cn/Article/CJFDTOTA ... 303029.htm
"In this study, a rat osteoblast-like cell line was used to observe the effect of fluorine on cell proliferation. The experimental results showed that when the fluorine content is 10μmol/L, it can promote the proliferation of bone cells, but it has an inhibitory effect over time. The results show that in addition to the experimental intensity, the action time is also important."
Yuan S, Xie Q, Lu F - "Changes of serotonin content and turnover rate in the hypothalamus of female rats during fluorosis" J China Med Univ. 20(Suppl):1-4 (1991) Neuroendocrine Research Laboratory, China Medical University, Shenyang, China. PFPC Library
"The content of 5-HT in the hypothalamus increased during subacute fluorosis but decreased during chronic fluorosis. These results might suggest that the release of 5-HT was blocked during fluorosis of short duration, while the synthesis of 5-HT was apparently affected after prolonged fluorosis." = Both subacute and chronic fluorosis decrease serotonin turnover in the hypothalamus. Content shifts with duration: ↑ in short-term, ↓ in long-term exposure.
Zhao W, Zhu H, Yu Z, Aoki K, Misumi J, Zhang X - "Long-term Effects of Various Iodine and Fluorine Doses on the Thyroid and Fluorosis in Mice" Endocr Regul 32 (2):63-70 (1998)
https://www.sav.sk/journals/endo/full/er0298a.pdf
"Under the ID conditions, fluorine in normal and excessive level increased thyroid radioiodine uptake after 100 days, but as the treatment with the same fluorine doses reached 150 days, the uptake was inhibited."
Zhong N, Ma Y, Meng X, Sowanou A, Wu L, Huang W, Gao Y, Pei J - "Effect of Fluoride in Drinking Water on Fecal Microbial Community in Rats" Biol Trace Elem Res 200(1):238-246 (2022) doi: 10.1007/s12011-021-02617-1
https://pubmed.ncbi.nlm.nih.gov/33576944/
"The results showed that fluoride did not significantly alter the diversity of fecal microbiota, but richness estimators (ACE and Chao) increased first, and then decreased with the increase of water fluoride. At the genus level, 150 mg/L fluoride significantly reduced the abundances of Roseburia and Clostridium sensu stricto, and 100 mg/L and 150 mg/L fluoride obviously increased the abundances of Unclassified Ruminococcaceaes and Unclassified Bdellovibrionales, respectively."
OTHER:
Burgstahler AW - "Paradoxical dose-response effects of fluoride [editorial]" Fluoride 35(3):143-7 (2002)
https://www.fluorideresearch.org/353/fi ... 43-147.pdf
PFAS:
Koskela A, Finnilä MA, Korkalainen M, Spulber S, Koponen J, Håkansson H, Tuukkanen J, Viluksela M - "Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation" Toxicol Appl Pharmacol 301:14-21 (2016). doi: 10.1016/j.taap.2016.04.002
https://www.sciencedirect.com/science/a ... via%3Dihub
"In osteoblasts, low concentrations of PFOA increased osteocalcin (OCN) expression and calcium secretion, but at PFOA concentrations of 100μM and above osteocalcin (OCN) expression and calcium secretion were decreased. The number of osteoclasts was increased at all PFOA concentrations tested and resorption activity dose-dependently increased from 0.1-1.0μM, but decreased at higher concentrations."
- Compare to Wang et al, 2020:
Wang J, Li G, Li Y, Zhao Y, Manthari RK, Wang J - "The Effects of Fluoride on the Gap-Junctional Intercellular Communication of Rats' Osteoblast" Biol Trace Elem Res 193(1):195-203 (2020). doi: 10.1007/s12011-019-01692-9
https://link.springer.com/article/10.10 ... 19-01692-9
"..the mRNA expressions of...OCN...were increased in the 0.01 mM NaF group and decreased in the 0.5 and 1 mM NaF groups."
https://pmc.ncbi.nlm.nih.gov/articles/PMC9012146/
"PFBS (10 and 100 μM) decreased cell migration and invasion, while PFBS (0.1 μM) significantly increased cell invasion but not migration."
Xing Y, Li Z, Wang J, Qu Y, Hu Q, Ji S, Chang X, Zhao F, Lv Y, Pan Y, Shi X, Dai J - "Associations between serum per- and polyfluoroalkyl substances and thyroid hormones in Chinese adults: A nationally representative cross-sectional study" Environ Int 184:108459 (2024). doi: 10.1016/j.envint.2024.108459
https://www.sciencedirect.com/science/a ... 202400045X
"Both individual PFASs and PFAS mixtures exhibited a significant inverse association with serum T3 and T4 levels, and displayed a positive association with the T4/T3 ratio...Specifically, for perfluoroheptane sulfonic acid (PFHpS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an initial decline in hormone levels was observed, followed by a slight increase when concentrations surpassed 0.7 ng/mL and 2.5 ng/mL, respectively. Sex-specific effects were more pronounced in females, and significant associations were observed predominantly in younger age groups."
Zhang S, Guo X, Lu S, Sang N, Li G, Xie P, Liu C, Zhang L, Xing Y - "Exposure to PFDoA causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae" Environ Pollut 235:974-982 (2018). doi: 10.1016/j.envpol.2018.01.015
https://pubmed.ncbi.nlm.nih.gov/29751401/
"Upregulation and downregulation of iodothyronine deiodinases (dio1) gene expression were observed upon the treatment of 1.2 mg/L and 6 mg/L PFDoA, respectively."
IP3R & Gq/11
Schmunk G, Boubion BJ, Smith IF, Parker I, Gargus JJ - "Shared functional defect in IP₃R-mediated calcium signaling in diverse monogenic autism syndromes" Transl Psychiatry 5(9):e643 (2015). doi: 10.1038/tp.2015.123
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068815/
"This was apparent in Ca(2+) signals evoked by G protein-coupled receptors and by photoreleased IP3 at the levels of both global and local elementary Ca(2+) events, suggesting fundamental defects in IP3R channel activity in ASD. Given the ubiquitous involvement of IP3R-mediated Ca(2+) signaling in neuronal excitability, synaptic plasticity, gene expression and neurodevelopment, we propose dysregulated IP3R signaling as a nexus where genes altered in ASD converge to exert their deleterious effect."
"This leads to biphasic regulation, such that small elevations of cytosolic Ca2+ induce channel opening, whereas larger elevations cause inactivation."
