Abstract
Fluoride is a natural element essential in minute quantities in human’s to maintain dental and skeletal health. However, the disease fluorosis manifests itself due to excessive fluoride intake mostly through drinking water and sometimes through food. At the cellular energetics level, fluoride is a known inhibitor of glycolysis. At the tissue level, the effect of fluoride has been more pronounced in the musculoskeletal systems due to its ability to retain fluoride. Fluoride alters dentinogenesis, thereby affecting the tooth enamel formation. In bones, fluoride alters the osteogenesis by replacing calcium, thus resulting in bone deformities. In skeletal muscles, high concentration and long term exposure to fluoride causes loss of muscle proteins leading to atrophy. Although fluorosis is quite a familiar problem, the exact molecular pathway is not yet clear. Extensive research on the effects of fluoride on various organs and its toxicity was reported. Indeed, it is clear that high and chronic exposure to fluoride causes cellular apoptosis. Accordingly, in this review, we have highlighted fluoride-mediated apoptosis via two vital pathways, mitochondrial-mediated and endoplasmic reticulum stress pathways. This review also elaborates on new cellular energetic, apoptotic pathways and therapeutic strategies targeted to treat fluorosis.
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Abbreviations
- ATP:
-
Adenosine triphosphate
- Caspase:
-
Cysteine aspartate specific protease
- PARP:
-
Poly (ADP-ribose) polymerase
- Cyt C:
-
Cytochrome C
- ER:
-
Endoplasmic reticulum
- Grp78:
-
Glucose regulated protein 78
- MFN:
-
Mitofusin
- MMP:
-
Mitochondrial membrane potential
- ROS:
-
Reactive oxygen species
- UPR:
-
Unfolded protein response
References
Daiwile AP, Tarale P, Sivanesan S, Naoghare PK, Bafana A, Parmar D, Kannan K (2019) Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis. Ecotoxicol Environ Saf 169:410–417
Urbansky ET (2002) Fate of fluorosilicate drinking water additives. Chem Rev 102:2837–2854
Srivastava S, Flora SJS (2020) Fluoride in drinking water and skeletal fluorosis: a review of the global impact. Curr Environ Health Rep 7:140–146
Chouhan S, Flora SJ (2010) Arsenic and fluoride: two major ground water pollutants. Indian J Exp Biol 48:666–678
Petersen PE, Ogawa H (2016) Prevention of dental caries through the use of fluoride–the WHO approach. Community Dent Health 33:66–68
Gevera P, Mouri H, Maronga G (2019) Occurrence of fluorosis in a population living in a high-fluoride groundwater area: Nakuru area in the Central Kenyan Rift Valley. Environ Geochem Health 41:829–840
Vani ML, Reddy KP (2000) Effects of fluoride accumulation on some enzymes of brain and gastrocnemius muscle of mice. Fluoride 33:17–26
Perera T, Ranasinghe S, Alles N, Waduge R (2018) Effect of fluoride on major organs with the different time of exposure in rats. Environ Health Prev Med 23:17
Gao Y, Liang C, Zhang J, Ma J, Wang J, Niu R, Tikka C, Wang Y, Wang J (2018) Combination of fluoride and SO2 induce DNA damage and morphological alterations in male rat kidney. Cell Physiol Biochem 50:734–744
Wang X, Lu X, Zhu R, Zhang K, Li S, Chen Z, Li L (2017) Betulinic acid induces apoptosis in differentiated PC12 cells via ROS-mediated mitochondrial pathway. Neurochem Res 42:1130–1140
Dec K, Łukomska A, Maciejewska D, Jakubczyk K, Baranowska-Bosiacka I, Chlubek D, Wąsik A, Gutowska I (2017) The influence of fluorine on the disturbances of homeostasis in the central nervous system. Biol Trace Elem Res 177:224–234
Abdel-Gawad FA, Ashmawy MH, Zaki SM, Abdel-Fatah GH (2014) Lung damage after long-term exposure of adult rats to sodium fluoride. Arch Med Sci 10:1035–1040
Adali MK, Varol E, Aksoy F, Icli A, Ersoy IH, Ozaydin M, Erdogan D, Dogan A (2013) Impaired heart rate recovery in patients with endemic fluorosis. Biol Trace Elem Res 152:310–315
Yan X, Wang L, Yang X, Qiu Y, Tian X, Lv Y, Tian F, Song G, Wang T (2017) Fluoride induces apoptosis in H9c2 cardiomyocytes via the mitochondrial pathway. Chemosphere 182:159–165
Song GH, Huang FB, Gao JP, Liu ML, Pang WB, Li W, Yan XY, Huo MJ, Yang X (2015) Effects of fluoride on DNA damage and caspase-mediated apoptosis in the liver of rats. Biol Trace Elem Res 166:173–182
Liang C, Gao Y, Zhao Y, Manthari RK, Ma J, Niu R, Wang J, Zhang J, Wang J (2018) Effects of fluoride and/or sulfur dioxide on morphology and DNA integrity in rats’ hepatic tissue. Biol Trace Elem Res 183:335–341
Zhao Y, Li Y, Wang J, Manthari RK, Wang J (2018) Fluoride induces apoptosis and autophagy through the IL-17 signaling pathway in mice hepatocytes. Arch Toxicol 92:3277–3289
Yang S-Y, Zhang L, Miao K-K, Qian W, Zhang Z-G (2013) Effects of selenium intervention on chronic fluorosis-induced renal cell apoptosis in rats. Biol Trace Elem Res 153:237–242
Liu J, Wang H-W, Zhao W-P, Li X-T, Lin L, Zhou B-H (2019) Induction of pathological changes and impaired expression of cytokines in developing female rat spleen after chronic excess fluoride exposure. Toxicol Ind Health 35:43–52
Shenoy PS, Sen U, Kapoor S, Ranade AV, Chowdhury CR, Bose B (2019) Sodium fluoride induced skeletal muscle changes: degradation of proteins and signaling mechanism. Environ Pollut 244:534–548
Li W, Jiang B, Cao X, Xie Y, Huang T (2017) Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated Caspase pathways. Chem Biol Interact 261:27–34
Jana L, Maity PP, Perveen H, Dash M, Jana S, Dey A, De SK, Chattopadhyay S (2018) Attenuation of utero-toxicity, metabolic dysfunction and inflammation by soy protein concentrate in rats exposed to fluoridated water: consequence of hyperlipidemia in parallel with hypohomocysteinemia. Environ Sci Pollut Res 25:36462–36473
Nelson EA, Halling CL, Buikstra JE (2019) Evidence of Skeletal Fluorosis at the Ray Site, Illinois, USA: a pathological assessment and discussion of environmental factors. Int J Paleopathol 26:48–60
Moimaz SA, Saliba O, Marques LB, Garbin CA, Saliba NA (2015) Dental fluorosis and its influence on children’s life. Braz Oral Res 29:1–7
Mendoza-Schulz A, Solano-Agama C, Arreola-Mendoza L, Reyes-Márquez B, Barbier O, Del Razo LM, Mendoza-Garrido ME (2009) The effects of fluoride on cell migration, cell proliferation, and cell metabolism in GH4C1 pituitary tumour cells. Toxicol Lett 190:179–186
Karube H, Nishitai G, Inageda K, Kurosu H, Matsuoka M (2009) NaF activates MAPKs and induces apoptosis in odontoblast-like cells. J Dent Res 88:461–465
Zhang M, Wang A, He W, He P, Xu B, Xia T, Chen X, Yang K (2007) Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in primary cultured hippocampal neurons. Toxicology 236:208–216
Amaechi BT, AbdulAzees PA, Alshareif DO, Shehata MA, Lima P, Abdollahi A, Kalkhorani PS, Evans V (2019) Comparative efficacy of a hydroxyapatite and a fluoride toothpaste for prevention and remineralization of dental caries in children. BDJ Open 5:18
Zhang X, Gao X, Li C, Luo X, Wang Y (2019) Fluoride contributes to the shaping of microbial community in high fluoride groundwater in Qiji County, Yuncheng City, China. Sci Rep 9:14488
Hamilton I (1990) Biochemical effects of fluoride on oral bacteria. J Dent Res 69:660–667
Zafar MS, Ahmed N (2015) Therapeutic roles of fluoride released from restorative dental materials. Fluoride 48:184
Gupta RK, Patel AK, Shah N, Chaudhary AK, Jha UK, Yadav UC, Gupta PK, Pakuwal U (2014) Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev 15:4405–4409
Besga A, Chyzhyk D, Gonzalez-Ortega I, Echeveste J, Graña-Lecuona M, Graña M, Gonzalez-Pinto A (2017) White matter tract integrity in Alzheimer’s disease vs. late onset bipolar disorder and its correlation with systemic inflammation and oxidative stress biomarkers. Front Aging Neurosci 9:179
Shivarajashankara Y, Shivashankara A, Rao SH (2001) Oxidative stress in children with endemic skeletal fluorosis. Fluoride 34(2):103–107
Yamaguti PM, Simões A, Ganzerla E, Souza DN, Nogueira FN, Nicolau J (2013) Effects of single exposure of sodium fluoride on lipid peroxidation and antioxidant enzymes in salivary glands of rats. Oxid Med Cell Longev 2013:674593
Hassan HA, Yousef MI (2009) Mitigating effects of antioxidant properties of black berry juice on sodium fluoride induced hepatotoxicity and oxidative stress in rats. Food Chem Toxicol 47:2332–2337
García-Montalvo EA, Reyes-Pérez H, Del Razo LM (2009) Fluoride exposure impairs glucose tolerance via decreased insulin expression and oxidative stress. Toxicology 263:75–83
Izquierdo-Vega JA, Sánchez-Gutiérrez M, Del Razo LM (2008) Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss. Toxicol Appl Pharmacol 230:352–357
Ying J, Xu J, Shen L, Mao Z, Liang J, Lin S, Yu X, Pan R, Yan C, Li S, Bao Q, Li P (2017) The effect of sodium fluoride on cell apoptosis and the mechanism of human lung BEAS-2B cells in vitro. Biol Trace Elem Res 179:59–69
Song Q, Gou WL, Zhang R (2016) FAM3A attenuates ER stress-induced mitochondrial dysfunction and apoptosis via CHOP-Wnt pathway. Neurochem Int 94:82–89
Wang J, Zhao Y, Cheng X, Li Y, Xu H, Manthari RK, Wang J (2018) Effects of different Ca(2+) level on fluoride-induced apoptosis pathway of endoplasmic reticulum in the rabbit osteoblast in vitro. Food Chem Toxicol 116:189–195
Nobes CD, Hall A (1995) Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81:53–62
Mittal M, Flora SJ (2006) Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice. Chem Biol Interact 162:128–139
Ghosh J, Das J, Manna P, Sil PC (2008) Cytoprotective effect of arjunolic acid in response to sodium fluoride mediated oxidative stress and cell death via necrotic pathway. Toxicol In Vitro 22:1918–1926
Miao L, Zhou M, Zhang X, Yuan C, Dong X, Zou X (2017) Effect of excess dietary fluoride on laying performance and antioxidant capacity of laying hens. Poult Sci 96:2200–2205
Peng W, Xu S, Zhang J, Zhang Y (2019) Vitamin C attenuates sodium fluoride-induced mitochondrial oxidative stress and apoptosis via Sirt1-SOD2 pathway in F9 cells. Biol Trace Elem Res 191:189–198
Jothiramajayam M, Sinha S, Ghosh M, Nag A, Jana A, Mukherjee A (2014) Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes. J Toxicol Environ Health A 77:1269–1280
Ding L, Li J, Li W, Fang Z, Li N, Wu S, Li J, Hong M (2018) p53- and ROS-mediated AIF pathway involved in TGEV-induced apoptosis. J Vet Med Sci 80(11):1775–1781
Ai T-J, Sun J-Y, Du L-J, Shi C, Li C, Sun X-N, Liu Y, Li L, Xia Z, Jia L (2018) Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes apoptosis of vascular smooth muscle cells through p53 and p62. Cell Death Differ 25:319–329
Yu G, Luo H, Zhang N, Wang Y, Li Y, Huang H, Liu Y, Hu Y, Liu H, Zhang J (2019) Loss of p53 sensitizes cells to palmitic acid-induced apoptosis by reactive oxygen species accumulation. Int J Mol Sci 20:6268
Deng H, Ikeda A, Cui H, Bartlett JD, Suzuki M (2019) MDM2-mediated p21 proteasomal degradation promotes fluoride toxicity in ameloblasts. Cells 8:436
Tu W, Zhang Q, Liu Y, Han L, Wang Q, Chen P, Zhang S, Wang A, Zhou X (2018) Fluoride induces apoptosis via inhibiting SIRT1 activity to activate mitochondrial p53 pathway in human neuroblastoma SH-SY5Y cells. Toxicol Appl Pharmacol 347:60–69
Suzuki M, Ikeda A, Bartlett JD (2018) Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation. Arch Toxicol 92:1283–1293
Dou G, Sreekumar PG, Spee C, He S, Ryan SJ, Kannan R, Hinton DR (2012) Deficiency of αB crystallin augments ER stress-induced apoptosis by enhancing mitochondrial dysfunction. Free Radic Biol Med 53:1111–1122
Flora S, Mittal M, Mishra D (2009) Co-exposure to arsenic and fluoride on oxidative stress, glutathione linked enzymes, biogenic amines and DNA damage in mouse brain. J Neurol Sci 285:198–205
Deng H, Kuang P, Cui H, Chen L, Fang J, Zuo Z, Deng J, Wang X, Zhao L (2016) Sodium fluoride induces apoptosis in cultured splenic lymphocytes from mice. Oncotarget 7:67880
Lee J-H, Jung J-Y, Jeong Y-J, Park J-H, Yang K-H, Choi N-K, Kim S-H, Kim W-J (2008) Involvement of both mitochondrial-and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts. Toxicology 243:340–347
Refsnes M, Schwarze PE, Holme JA, Laêg M (2003) Fluoride-induced apoptosis in human epithelial lung cells (A549 cells): role of different G protein-linked signal systems. Hum Exp Toxicol 22:111–123
Ying J, Xu J, Shen L, Mao Z, Liang J, Lin S, Yu X, Pan R, Yan C, Li S (2017) The effect of sodium fluoride on cell apoptosis and the mechanism of human lung BEAS-2B cells in vitro. Biol Trace Elem Res 179:59–69
Zhou B-h, Tan P-p, Jia L-s, Zhao W-p, Wang J-c, Wang H-w (2018) PI3K/AKT signaling pathway involvement in fluoride-induced apoptosis in C2C12 cells. Chemosphere 199:297–302
Sun Z, Niu R, Wang B, Jiao Z, Wang J, Zhang J, Wang S, Wang J (2011) Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo. Arch Toxicol 85:1441–1452
Ni J, Li Y, Zhang W, Shu R, Zhong Z (2018) Sodium fluoride causes oxidative stress and apoptosis in cementoblasts. Chem Biol Interact 294:34–39
Fu X, Xie F-N, Dong P, Li Q-C, Yu G-Y, Xiao R (2016) High-dose fluoride impairs the properties of human embryonic stem cells via JNK signaling. PLoS ONE 11:e0148819
Ma Y, Zhang K, Ren F, Wang J (2017) Developmental fluoride exposure influenced rat’s splenic development and cell cycle via disruption of the ERK signal pathway. Chemosphere 187:173–180
Zhang Y-L, Luo Q, Deng Q, Li T, Li Y, Zhang Z-L, Zhong J-J (2015) Genes associated with sodium fluoride-induced human osteoblast apoptosis. Int J Clin Exp Med 8:13171
Gao J, Wang Y, Xu G, Wei J, Chang K, Tian X, Liu M, Yan X, Huo M, Song G (2019) Selenium attenuates apoptosis and p-AMPK expressions in fluoride-induced NRK-52E cells. Environ Sci Pollut Res 26:15685–15697
Gu X, Wang Z, Gao J, Han D, Zhang L, Chen P, Luo G, Han B (2019) SIRT1 suppresses p53-dependent apoptosis by modulation of p21 in osteoblast-like MC3T3-E1 cells exposed to fluoride. Toxicol In Vitro 57:28–38
Hu Y, Shao Z, Cai X, Liu Y, Shen M, Yao Y, Yuan T, Wang W, Ding F, Xiong L (2019) Mitochondrial pathway is involved in advanced glycation end products-induced apoptosis of rabbit annulus fibrosus cells. Spine 44:E585
Wu H-Y, Huang C-H, Lin Y-H, Wang C-C, Jan T-R (2018) Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production. Free Radic Biol Med 124:311–318
Chen Y, Chen S, Liang H, Yang H, Liu L, Zhou K, Xu L, Liu J, Yun L, Lai B (2018) Bcl-2 protects TK6 cells against hydroquinone-induced apoptosis through PARP-1 cytoplasm translocation and stabilizing mitochondrial membrane potential. Environ Mol Mutagen 59:49–59
Yan H, Du J, Chen X, Yang B, He Q, Yang X, Luo P (2019) ROS-dependent DNA damage contributes to crizotinib-induced hepatotoxicity via the apoptotic pathway. Toxicol Appl Pharmacol 383:114768
Wang H-W, Zhao W-P, Liu J, Tan P-P, Tian W-S, Zhou B-H (2017) ATP5J and ATP5H proactive expression correlates with cardiomyocyte mitochondrial dysfunction induced by fluoride. Biol Trace Elem Res 180:63–69
Araujo TT, Pereira HABS, Dionizio A, de Carmo Sanchez C, de Souza Carvalho T, da Silva Fernandes M, Buzalaf MAR (2019) Changes in energy metabolism induced by fluoride: Insights from inside the mitochondria. Chemosphere 236:124357
Zhou G, Tang S, Yang L, Niu Q, Chen J, Xia T, Wang S, Wang M, Zhao Q, Liu L (2019) Effects of long-term fluoride exposure on cognitive ability and the underlying mechanisms: role of autophagy and its association with apoptosis. Toxicol Appl Pharmacol 378:114608
Brown JL, Rosa-Caldwell ME, Lee DE, Blackwell TA, Brown LA, Perry RA, Haynie WS, Hardee JP, Carson JA, Wiggs MP (2017) Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice. J Cachexia Sarcopenia Muscle 8:926–938
Bertholet AM, Delerue T, Millet AM, Moulis MF, David C, Daloyau M, Arnauné-Pelloquin L, Davezac N, Mils V, Miquel MC, Rojo M, Belenguer P (2016) Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity. Neurobiol Dis 90:3–19
Zhao W-P, Wang H-W, Liu J, Zhang Z-H, Zhu S-Q, Zhou B-H (2019) Mitochondrial respiratory chain complex abnormal expressions and fusion disorder are involved in fluoride-induced mitochondrial dysfunction in ovarian granulosa cells. Chemosphere 215:619–625
Zhao Q, Niu Q, Chen J, Xia T, Zhou G, Li P, Dong L, Xu C, Tian Z, Luo C, Liu L, Zhang S, Wang A (2019) Roles of mitochondrial fission inhibition in developmental fluoride neurotoxicity: mechanisms of action in vitro and associations with cognition in rats and children. Arch Toxicol 93:709–726
Zhou X, Chen Z, Zhong W, Yu R, He L (2019) Effect of fluoride on PERK-Nrf2 signaling pathway in mouse ameloblasts. Hum Exp Toxicol 38:833–845
Qin S-L, Deng J, Lou D-D, Yu W-F, Pei J, Guan Z-Z (2015) The decreased expression of mitofusin-1 and increased fission-1 together with alterations in mitochondrial morphology in the kidney of rats with chronic fluorosis may involve elevated oxidative stress. J Trace Elem Med Biol 29:263–268
Aulestia FJ, Groeling J, Bomfim GHS, Costiniti V, Manikandan V, Chaloemtoem A, Concepcion AR, Li Y, Wagner LE 2nd, Idaghdour Y, Yule DI, Lacruz RS (2020) Fluoride exposure alters Ca(2+) signaling and mitochondrial function in enamel cells. Sci Signal 13:eaay0086
Yang T, Zhang Y, Li Y, Hao Y, Zhou M, Dong N, Duan X (2013) High amounts of fluoride induce apoptosis/cell death in matured ameloblast-like LS8 cells by downregulating Bcl-2. Arch Oral Biol 58:1165–1173
Sakthivel R, Malar DS, Devi KP (2018) Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential. Biomed Pharmacother 105:742–752
Tan P-P, Zhou B-H, Zhao W-P, Jia L-S, Liu J, Wang H-W (2018) Mitochondria-mediated pathway regulates C2C12 cell apoptosis induced by fluoride. Biol Trace Elem Res 185:440–447
Comelli M, Di Pancrazio F, Mavelli I (2003) Apoptosis is induced by decline of mitochondrial ATP synthesis in erythroleukemia cells. Free Radical Biol Med 34:1190–1199
Sun Z, Zhang W, Xue X, Zhang Y, Niu R, Li X, Li B, Wang X, Wang J (2016) Fluoride decreased the sperm ATP of mice through inhabiting mitochondrial respiration. Chemosphere 144:1012–1017
Sakamuru S, Attene-Ramos MS, Xia M (2016) Mitochondrial membrane potential assay. In: Zhu H, Xia M (eds) High-throughput screening assays in toxicology. Methods in molecular biology, vol 1473. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6346-1_2
Lee J-Y, Lim W, Ham J, Kim J, You S, Song G (2019) Ivermectin induces apoptosis of porcine trophectoderm and uterine luminal epithelial cells through loss of mitochondrial membrane potential, mitochondrial calcium ion overload, and reactive oxygen species generation. Pestic Biochem Physiol 159:144–153
Ha TK, Hansen AH, Kildegaard HF, Lee GM (2019) BiP inducer X: an ER stress inhibitor for enhancing recombinant antibody production in CHO cell culture. Biotechnol J 14:1900130
Zhang C, Ge J, Lv M, Zhang Q, Talukder M, Li J-L (2020) Selenium prevent cadmium-induced hepatotoxicity through modulation of endoplasmic reticulum-resident selenoproteins and attenuation of endoplasmic reticulum stress. Environ Pollut 260:113873
Deng H, Kuang P, Cui H, Chen L, Luo Q, Fang J, Zuo Z, Deng J, Wang X, Zhao L (2016) Sodium fluoride (NaF) induces the splenic apoptosis via endoplasmic reticulum (ER) stress pathway in vivo and in vitro. Aging 8:3552
Nascimento AC, Erustes AG, Reckziegel P, Bincoletto C, Ureshino RP, Pereira GJ, Smaili SS (2020) α-Synuclein overexpression induces lysosomal dysfunction and autophagy impairment in human neuroblastoma SH-SY5Y. Neurochem Res 45:2749–2761
Zhu P, Hu S, Jin Q, Li D, Tian F, Toan S, Li Y, Zhou H, Chen Y (2018) Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: a mechanism involving calcium overload/XO/ROS/mPTP pathway. Redox Biol 16:157–168
Zhang Y, Zhang K, Ma L, Gu H, Li J, Lei S (2016) Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts. Arch Oral Biol 69:95–101
Kopp MC, Larburu N, Durairaj V, Adams CJ, Ali MM (2019) UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor. Nat Struct Mol Biol 26:1053–1062
Ghaderi S, Ahmadian S, Soheili ZS, Ahmadieh H, Samiei S, Kheitan S, Pirmardan ER (2018) AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress. J Cell Biochem 119:1355–1367
Song J-Y, Wang X-G, Zhang Z-Y, Che L, Fan B, Li G-Y (2020) Endoplasmic reticulum stress and the protein degradation system in ophthalmic diseases. PeerJ 8:e8638–e8638
Li J, Zhao L, Zhao X, Wang P, Liu Y, Ruan J (2018) Foxo1 attenuates NaF-induced apoptosis of LS8 cells through the JNK and mitochondrial pathways. Biol Trace Elem Res 181:104–111
Dong N, Feng J, Xie J, Tian X, Li M, Liu P, Zhao Y, Wei C, Gao Y, Li B, Qiu Y, Yan X (2020) Co-exposure to arsenic-fluoride results in endoplasmic reticulum stress-induced apoptosis through the perk signaling pathway in the liver of offspring rats. Biol Trace Elem Res 197:192–201
Ke L, Zheng X, Sun Y, Ouyang W, Zhang Z (2016) Effects of sodium fluoride on lipid peroxidation and PARP, XBP-1 expression in PC12 cell. Biol Trace Elem Res 173:161–167
Delbrel E, Soumare A, Naguez A, Label R, Bernard O, Bruhat A, Fafournoux P, Tremblais G, Marchant D, Gille T (2018) HIF-1α triggers ER stress and CHOP-mediated apoptosis in alveolar epithelial cells, a key event in pulmonary fibrosis. Sci Rep 8:1–14
Liu H, Zeng Q, Cui Y, Zhao L, Zhang L, Fu G, Hou C, Zhang S, Yu L, Jiang C (2014) The role of the IRE1 pathway in excessive iodide-and/or fluoride-induced apoptosis in Nthy-ori 3–1 cells in vitro. Toxicol Lett 224:341–348
Wei W, Gao Y, Wang C, Zhao L, Sun D (2013) Excessive fluoride induces endoplasmic reticulum stress and interferes enamel proteinases secretion. Environ Toxicol 28:332–341
Liu X, Huang R, Gao Y, Gao M, Ruan J, Gao J (2021) Calcium mitigates fluoride-induced kallikrein 4 inhibition via PERK/eIF2α/ATF4/CHOP endoplasmic reticulum stress pathway in ameloblast-lineage cells. Arch Oral Biol 125:105093
Thippeswamy HM, Devananda D, Nanditha Kumar M, Wormald MM, Prashanth SN (2021) The association of fluoride in drinking water with serum calcium, vitamin D and parathyroid hormone in pregnant women and newborn infants. Eur J Clin Nutr 75(1):151–159
Bondu JD, Seshadri M, Selvakumar R, Fleming JJ (2019) Effects of fluoride on bone in an animal model of vitamin D deficiency. Indian J Clin Biochem 34:60–67
Tyszka-Czochara M, Bukowska-Strakova K, Kocemba-Pilarczyk KA, Majka M (2018) Caffeic acid targets AMPK signaling and regulates tricarboxylic acid cycle anaplerosis while Metformin downregulates HIF-1α-induced glycolytic enzymes in human cervical squamous cell carcinoma lines. Nutrients 10:841
Maurya DK, Devasagayam TPA (2010) Antioxidant and prooxidant nature of hydroxycinnamic acid derivatives ferulic and caffeic acids. Food Chem Toxicol 48:3369–3373
Yang WS, Jeong D, Yi YS, Park JG, Seo H, Moh SH, Hong S, Cho JY (2013) IRAK1/4-targeted anti-inflammatory action of caffeic acid. Mediat Inflamm 2013:518183
Figueiredo-Rinhel AS, Kabeya LM, Bueno PC, Jorge-Tiossi RF, Azzolini AEC, Bastos JK, Lucisano-Valim YM (2013) Inhibition of the human neutrophil oxidative metabolism by Baccharis dracunculifolia DC (Asteraceae) is influenced by seasonality and the ratio of caffeic acid to other phenolic compounds. J Ethnopharmacol 150:655–664
Pari L, Prasath A (2008) Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats. Chem Biol Interact 173:77–83
Kanagaraj VV, Panneerselvam L, Govindarajan V, Ameeramja J, Perumal E (2015) Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in rats: a possible mechanism. BioFactors 41:90–100
Costa-Rodrigues J, Fernandes MH, Pinho O, Monteiro PRR (2018) Modulation of human osteoclastogenesis and osteoblastogenesis by lycopene. J Nutr Biochem 57:26–34
Zhang Z, Zhou B, Wang H, Wang F, Song Y, Liu S, Xi S (2014) Maize purple plant pigment protects against fluoride-induced oxidative damage of liver and kidney in rats. Int J Environ Res Public Health 11:1020–1033
Annunziata G, Maisto M, Schisano C, Ciampaglia R, Daliu P, Narciso V, Tenore GC, Novellino E (2018) Colon bioaccessibility and antioxidant activity of white, green and black tea polyphenols extract after in vitro simulated gastrointestinal digestion. Nutrients 10:1711
Li B-Y, Gao Y-H, Pei J-R, Yang Y-M, Zhang W, Sun D-J (2017) ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis. Int J Mol Med 39:1155–1163
Papaioannou EH, Liakopoulou-Kyriakides M, Karabelas AJ (2016) Natural origin lycopene and its “green” downstream processing. Crit Rev Food Sci Nutr 56:686–709
Nabavi SM, Nabavi SF, Moghaddam AH, Setzer WN, Mirzaei M (2012) Effect of silymarin on sodium fluoride-induced toxicity and oxidative stress in rat cardiac tissues. An Acad Bras Cienc 84(4):1121–1126
Chouhan S, Yadav A, Kushwah P et al (2011) Silymarin and quercetin abrogates fluoride induced oxidative stress and toxic effects in rats. Mol Cell Toxicol 7:25
Dey S, Swarup D, Saxena A, Dan A (2011) In vivo efficacy of tamarind (Tamarindus indica) fruit extract on experimental fluoride exposure in rats. Res Vet Sci 91(3):422–425
Rupal A, Vasant A, Narasimhacharya VRL (2011) Antihyperglycemic and Antihyperlipidemic effects of Mangifera Indica L. in fluoride induced toxicity. Pharmacologyonline 3:265–274
Acknowledgements
The authors would like to thank Dr.Shivashankara A.R., Associate Professor in Biochemistry, Father Muller Medical College, Mangalore, for his suggestions to improve the scientific content in this article. The authors would also like to thank Yenepoya Research Centre, Yenepoya Deemed to be University, for providing the online library resources for writing this perspective article.
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AHN: Contributed in writing the paper and conceived the artwork. BB and SSP: Contributed in writing, correcting the text, finalizing the manuscript. All authors read and approved the manuscript.
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Nagendra, A.H., Bose, B. & Shenoy P, S. Recent advances in cellular effects of fluoride: an update on its signalling pathway and targeted therapeutic approaches. Mol Biol Rep 48, 5661–5673 (2021). https://doi.org/10.1007/s11033-021-06523-6
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DOI: https://doi.org/10.1007/s11033-021-06523-6