{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:09:05Z","timestamp":1772003345947,"version":"3.50.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005639","name":"Universidade De S\u00e3o Paulo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005639","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Histol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fluoride is commonly used in dentistry to prevent dental caries, however, excessive exposure may pose risks to soft tissues, particularly the kidneys, which are responsible for approximately 60% of fluoride excretion. Diabetic nephropathy, a major complication of diabetes mellitus, may share pathogenic pathways with fluoride-induced renal toxicity. However, the combined effects of chronic hyperglycemia and fluoride exposure on kidney cells remain poorly understood. This study investigated the effects of fluoride on murine renal tubular epithelial cells (M-1) and on murine kidneys under normal and hyperglycemic conditions. M-1 cells were cultured under high-glucose conditions (22.5 mM) and\/or treated with fluoride (1 \u00b5M or 5 \u00b5M) for 24 to 72\u00a0h. Diabetic C57BL\/6J mice received drinking water containing fluoride (10 mgF\/L or 50 mgF\/L) for 21 days. Evaluations included cell viability and morphology in vitro, collagen deposition in renal tissue by birefringence analysis, and expression of the kidney injury marker KIM-1 by immunofluorescence in both models. M-1 cells exposed to fluoride alone showed increased viability at 72\u00a0h, while KIM-1 expression was elevated in high-glucose and high-glucose\u2009+\u20091 \u00b5M fluoride conditions, suggesting a stress or adaptive response. In diabetic mice, glomerular collagen accumulation, indicative of early fibrosis, was observed but attenuated by fluoride treatment. However, high KIM-1 levels in fluoride-treated diabetic mice, particularly at the higher dose, indicated potential kidney injury. These results highlight a complex, dual role of F in the diabetic kidney, potentially protecting against glomerular fibrosis while exacerbating tubular injury at high doses. Careful monitoring of F exposure is needed, especially in areas with endemic fluorosis and high chronic kidney disease risk.<\/jats:p>","DOI":"10.1007\/s10735-025-10670-6","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T06:38:32Z","timestamp":1768199912000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined effects of chronic high glucose and fluoride exposure on kidney cells: exploratory in vitro and in vivo study"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5970-9714","authenticated-orcid":false,"given":"Laura","family":"Ribeiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-2546","authenticated-orcid":false,"given":"Helo\u00edsa Aparecida Barbosa da Silva","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-661X","authenticated-orcid":false,"given":"Juliana Sanches","family":"Trevizol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-2754","authenticated-orcid":false,"given":"Aislan Quintiliano","family":"Delgado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-5974","authenticated-orcid":false,"given":"T\u00e2nia Mary","family":"Cestari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5985-3951","authenticated-orcid":false,"given":"Mar\u00edlia Afonso Rabelo","family":"Buzalaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-5960","authenticated-orcid":false,"given":"Rodrigo Cardoso","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4503-3108","authenticated-orcid":false,"given":"Claudia Cristina","family":"Biguetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"10670_CR1","doi-asserted-by":"publisher","unstructured":"Abid Khan F, Fatima SS, Khan GM, Shahid S (2019). Evaluation of kidney injury molecule-1 as a disease progression biomarker in diabetic nephropathy: KIM-1 and Diabetic Nephropathy. Pakistan Journal of Medical Sciences, 35(4). https:\/\/doi.org\/10.12669\/pjms.35.4.154","DOI":"10.12669\/pjms.35.4.154"},{"issue":"4","key":"10670_CR2","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jscs.2010.05.004","volume":"14","author":"EA Al Omireeni","year":"2010","unstructured":"Al Omireeni EA, Siddiqi NJ, Alhomida AS (2010) Biochemical and histological studies on the effect of sodium fluoride on rat kidney collagen. J Saudi Chem Soc 14(4):413\u2013416. https:\/\/doi.org\/10.1016\/j.jscs.2010.05.004","journal-title":"J Saudi Chem Soc"},{"issue":"5","key":"10670_CR3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2220\/biomedres.30.271","volume":"30","author":"Y Arakawa","year":"2009","unstructured":"Arakawa Y, Bhawal UK, Ikoma T, Kimoto K, Kuroha K, Kubota T, Hamada N, Kubota E, Arakawa H (2009) Low concentration fluoride stimulates cell motility of epithelial cells in vitro. Biomed Res 30(5):271\u2013277. https:\/\/doi.org\/10.2220\/biomedres.30.271","journal-title":"Biomed Res"},{"key":"10670_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2019.124357","volume":"236","author":"TT Araujo","year":"2019","unstructured":"Araujo TT, Barbosa Silva Pereira HA, Dionizio A, Sanchez CDC, De Souza Carvalho T, Da Silva Fernandes M, Rabelo Buzalaf MA (2019) Changes in energy metabolism induced by fluoride: insights from inside the mitochondria. Chemosphere 236:124357. https:\/\/doi.org\/10.1016\/j.chemosphere.2019.124357","journal-title":"Chemosphere"},{"issue":"2","key":"10670_CR5","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.cbi.2010.07.011","volume":"188","author":"O Barbier","year":"2010","unstructured":"Barbier O, Arreola-Mendoza L, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188(2):319\u2013333. https:\/\/doi.org\/10.1016\/j.cbi.2010.07.011","journal-title":"Chem Biol Interact"},{"key":"10670_CR6","doi-asserted-by":"publisher","DOI":"10.3389\/fmats.2021.651970","volume":"8","author":"CC Biguetti","year":"2021","unstructured":"Biguetti CC, Cavalla F, Fonseca AC, Tabanez AP, Siddiqui DA, Wheelis SE, Taga R, Fakhouri WD, Silva RM, Rodrigues DC, Garlet GP (2021) Effects of titanium corrosion products on in vivo biological response: a basis for the understanding of osseointegration failures mechanisms. Frontiers in Materials 8:651970. https:\/\/doi.org\/10.3389\/fmats.2021.651970","journal-title":"Frontiers in Materials"},{"key":"10670_CR7","doi-asserted-by":"publisher","unstructured":"Biguetti CC, Cavalla F, Silveira EM, Fonseca AC, Vieira AE, Tabanez AP, Rodrigues DC, Trombone APF, Garlet GP (2018). Oral implant osseointegration model in C57Bl\/6 mice: Microtomographic, histological, histomorphometric and molecular characterization. J Appl Oral Sci 26(0). https:\/\/doi.org\/10.1590\/1678-7757-2017-0601","DOI":"10.1590\/1678-7757-2017-0601"},{"key":"10670_CR8","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.3389\/fimmu.2018.01804","volume":"9","author":"CC Biguetti","year":"2018","unstructured":"Biguetti CC, Vieira AE, Cavalla F, Fonseca AC, Colavite PM, Silva RM, Trombone APF, Garlet GP (2018b) CCR2 contributes to F4\/80+ cells migration along intramembranous bone healing in maxilla, but its deficiency does not critically affect the healing outcome. Front Immunol 9:1804. https:\/\/doi.org\/10.3389\/fimmu.2018.01804","journal-title":"Front Immunol"},{"issue":"2","key":"10670_CR9","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1177\/0022034517750850","volume":"29","author":"MAR Buzalaf","year":"2018","unstructured":"Buzalaf MAR (2018) Review of fluoride intake and appropriateness of current guidelines. Adv Dent Res 29(2):157\u2013166. https:\/\/doi.org\/10.1177\/0022034517750850","journal-title":"Adv Dent Res"},{"key":"10670_CR10","unstructured":"Buzalaf MAR, Cury JA, Whitford GM (2001). Fluoride Exposures and Dental Fluorosis: A Literature Review. J A"},{"issue":"6","key":"10670_CR11","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.3892\/etm.2016.3194","volume":"11","author":"X Chen","year":"2016","unstructured":"Chen X, Wang D-D, Wei T, He S-M, Zhang G-Y, Wei Q-L (2016) Effects of astragalosides from Radix Astragali on high glucose-induced proliferation and extracellular matrix accumulation in glomerular mesangial cells. Exp Ther Med 11(6):2561\u20132566. https:\/\/doi.org\/10.3892\/etm.2016.3194","journal-title":"Exp Ther Med"},{"issue":"3","key":"10670_CR12","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41581-024-00902-5","volume":"21","author":"V De Gregorio","year":"2025","unstructured":"De Gregorio V, Barua M, Lennon R (2025) Collagen formation, function and role in kidney disease. Nat Rev Nephrol 21(3):200\u2013215. https:\/\/doi.org\/10.1038\/s41581-024-00902-5","journal-title":"Nat Rev Nephrol"},{"key":"10670_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.140419","volume":"741","author":"A Dionizio","year":"2020","unstructured":"Dionizio A, Melo CGS, Sabino-Arias IT, Araujo TT, Ventura TMO, Leite AL, Souza SRG, Santos EX, Heubel AD, Souza JG, Perles JVCM, Zanoni JN, Buzalaf MAR (2020) Effects of acute fluoride exposure on the jejunum and ileum of rats: insights from proteomic and enteric innervation analysis. Sci Total Environ 741:140419. https:\/\/doi.org\/10.1016\/j.scitotenv.2020.140419","journal-title":"Sci Total Environ"},{"issue":"1","key":"10670_CR14","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s12011-018-1542-4","volume":"190","author":"A Dionizio","year":"2019","unstructured":"Dionizio A, Pereira HABS, Araujo TT, Sabino-Arias IT, Fernandes MS, Oliveira KA, Raymundo FS, Cestari TM, Nogueira FN, Carvalho RA, Buzalaf MAR (2019) Effect of duration of exposure to fluoride and type of diet on lipid parameters and de novo lipogenesis. Biol Trace Elem Res 190(1):157\u2013171. https:\/\/doi.org\/10.1007\/s12011-018-1542-4","journal-title":"Biol Trace Elem Res"},{"issue":"10","key":"10670_CR15","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1007\/s00125-018-4656-5","volume":"61","author":"C Ghezzi","year":"2018","unstructured":"Ghezzi C, Loo DDF, Wright EM (2018) Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2. Diabetologia 61(10):2087\u20132097. https:\/\/doi.org\/10.1007\/s00125-018-4656-5","journal-title":"Diabetologia"},{"key":"10670_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2011\/416254","volume":"2011","author":"ER Gilbert","year":"2011","unstructured":"Gilbert ER, Fu Z, Liu D (2011) Development of a nongenetic mouse model of type 2 diabetes. Exp Diabetes Res 2011:1\u201312. https:\/\/doi.org\/10.1155\/2011\/416254","journal-title":"Exp Diabetes Res"},{"issue":"6","key":"10670_CR17","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1159\/000445598","volume":"38","author":"R Gou","year":"2016","unstructured":"Gou R, Chen J, Sheng S, Wang R, Fang Y, Yang Z, Wang L, Tang L (2016) KIM-1 mediates high glucose-induced autophagy and apoptosis in renal tubular epithelial cells. Cell Physiol Biochem 38(6):2479\u20132488. https:\/\/doi.org\/10.1159\/000445598","journal-title":"Cell Physiol Biochem"},{"issue":"3","key":"10670_CR18","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1159\/000016312","volume":"9","author":"G Gstraunthaler","year":"1999","unstructured":"Gstraunthaler G, Seppi T, Pfaller W (1999) Impact of culture conditions, culture media volumes, and glucose content on metabolic properties of renal epithelial cell cultures. Cell Physiol Biochem 9(3):150\u2013172. https:\/\/doi.org\/10.1159\/000016312","journal-title":"Cell Physiol Biochem"},{"issue":"3","key":"10670_CR19","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1177\/0748233713502843","volume":"32","author":"I Gutowska","year":"2016","unstructured":"Gutowska I, Baranowska-Bosiacka I, Siwiec E, Szczuko M, Kolasa A, Kondarewicz A, Rybicka M, Dunaj-Sta\u0144czyk M, Wiernicki I, Chlubek D, Stachowska E (2016) Lead enhances fluoride influence on apoptotic processes in the HepG2 liver cell line. Toxicol Ind Health 32(3):517\u2013525. https:\/\/doi.org\/10.1177\/0748233713502843","journal-title":"Toxicol Ind Health"},{"issue":"3","key":"10670_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.2004","volume":"7","author":"MJ Hossain","year":"2024","unstructured":"Hossain MJ, Al\u2010Mamun Md, Islam MR (2024) Diabetes mellitus, the fastest growing global public health concern: early detection should be focused. Health Sci Rep 7(3):e2004. https:\/\/doi.org\/10.1002\/hsr2.2004","journal-title":"Health Sci Rep"},{"issue":"9","key":"10670_CR21","doi-asserted-by":"publisher","first-page":"4023","DOI":"10.1172\/JCI45361","volume":"123","author":"BD Humphreys","year":"2013","unstructured":"Humphreys BD, Xu F, Sabbisetti V, Grgic I, Naini SM, Wang N, Chen G, Xiao S, Patel D, Henderson JM, Ichimura T, Mou S, Soeung S, McMahon AP, Kuchroo VK, Bonventre JV (2013) Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis. J Clin Invest 123(9):4023\u20134035. https:\/\/doi.org\/10.1172\/JCI45361","journal-title":"J Clin Invest"},{"issue":"3","key":"10670_CR22","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.trre.2010.02.002","volume":"24","author":"W Huo","year":"2010","unstructured":"Huo W, Zhang K, Nie Z, Li Q, Jin F (2010) Kidney injury molecule-1 (KIM-1): a novel kidney-specific injury molecule playing potential double-edged functions in kidney injury. Transplant Rev 24(3):143\u2013146. https:\/\/doi.org\/10.1016\/j.trre.2010.02.002","journal-title":"Transplant Rev"},{"issue":"3","key":"10670_CR23","doi-asserted-by":"publisher","first-page":"F552","DOI":"10.1152\/ajprenal.00285.2002","volume":"286","author":"T Ichimura","year":"2004","unstructured":"Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV (2004) Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 286(3):F552\u2013F563. https:\/\/doi.org\/10.1152\/ajprenal.00285.2002","journal-title":"Am J Physiol Renal Physiol"},{"key":"10670_CR24","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.taap.2018.05.027","volume":"352","author":"MI Jim\u00e9nez-C\u00f3rdova","year":"2018","unstructured":"Jim\u00e9nez-C\u00f3rdova MI, C\u00e1rdenas-Gonz\u00e1lez M, Aguilar-Madrid G, Sanchez-Pe\u00f1a LC, Barrera-Hern\u00e1ndez \u00c1, Dom\u00ednguez-Guerrero IA, Gonz\u00e1lez-Horta C, Barbier OC, Del Razo LM (2018) Evaluation of kidney injury biomarkers in an adult Mexican population environmentally exposed to fluoride and low arsenic levels. Toxicol Appl Pharmacol 352:97\u2013106. https:\/\/doi.org\/10.1016\/j.taap.2018.05.027","journal-title":"Toxicol Appl Pharmacol"},{"issue":"4","key":"10670_CR25","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1007\/s00204-020-02687-5","volume":"94","author":"NR Johnston","year":"2020","unstructured":"Johnston NR, Strobel SA (2020) Principles of fluoride toxicity and the cellular response: a review. Arch Toxicol 94(4):1051\u20131069. https:\/\/doi.org\/10.1007\/s00204-020-02687-5","journal-title":"Arch Toxicol"},{"issue":"2","key":"10670_CR26","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.cbi.2009.03.009","volume":"180","author":"CAN Kobayashi","year":"2009","unstructured":"Kobayashi CAN, Leite AL, Silva TL, Santos LD, Nogueira FCS, Oliveira RC, Palma MS, Domont GB, Buzalaf MAR (2009) Proteomic analysis of kidney in rats chronically exposed to fluoride. Chem Biol Interact 180(2):305\u2013311. https:\/\/doi.org\/10.1016\/j.cbi.2009.03.009","journal-title":"Chem Biol Interact"},{"issue":"7","key":"10670_CR27","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1007\/s12011-021-02927-4","volume":"200","author":"R Korkmaz","year":"2022","unstructured":"Korkmaz R, Y\u00fcksek V, Dede S (2022) The effects of sodium fluoride (NaF) treatment on the PI3K\/Akt signal pathway in NRK-52E cells. Biol Trace Elem Res 200(7):3294\u20133302. https:\/\/doi.org\/10.1007\/s12011-021-02927-4","journal-title":"Biol Trace Elem Res"},{"key":"10670_CR28","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.3389\/fimmu.2019.01223","volume":"10","author":"Y Lei","year":"2019","unstructured":"Lei Y, Devarapu SK, Motrapu M, Cohen CD, Lindenmeyer MT, Moll S, Kumar SV, Anders H-J (2019) Interleukin-1\u03b2 inhibition for chronic kidney disease in obese mice with type 2 diabetes. Front Immunol 10:1223. https:\/\/doi.org\/10.3389\/fimmu.2019.01223","journal-title":"Front Immunol"},{"issue":"9","key":"10670_CR29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106646","volume":"9","author":"A Lima Leite","year":"2014","unstructured":"Lima Leite A, Gualiume Vaz Madureira Lobo J, Barbosa Da Silva Pereira HA, Silva Fernandes M, Martini T, Zucki F, Sumida DH, Rigalli A, Buzalaf MAR (2014) Proteomic analysis of gastrocnemius muscle in rats with streptozotocin-induced diabetes and chronically exposed to fluoride. PLoS ONE 9(9):e106646. https:\/\/doi.org\/10.1371\/journal.pone.0106646","journal-title":"PLoS ONE"},{"issue":"7","key":"10670_CR30","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1177\/0022034515581186","volume":"94","author":"JGVM Lobo","year":"2015","unstructured":"Lobo JGVM, Leite AL, Pereira HABS, Fernandes MS, Peres-Buzalaf C, Sumida DH, Rigalli A, Buzalaf MAR (2015) Low-level fluoride exposure increases insulin sensitivity in experimental diabetes. J Dent Res 94(7):990\u2013997. https:\/\/doi.org\/10.1177\/0022034515581186","journal-title":"J Dent Res"},{"issue":"2","key":"10670_CR31","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1007\/s12011-010-8690-5","volume":"140","author":"M Lupo","year":"2011","unstructured":"Lupo M, Buzalaf MAR, Rigalli A (2011) Effect of fluoridated water on plasma insulin levels and glucose homeostasis in rats with renal deficiency. Biol Trace Elem Res 140(2):198\u2013207. https:\/\/doi.org\/10.1007\/s12011-010-8690-5","journal-title":"Biol Trace Elem Res"},{"key":"10670_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2024.127506","volume":"86","author":"S Meenakshi","year":"2024","unstructured":"Meenakshi S, Bahekar T, Narapaka PK, Pal B, Prakash V, Dhingra S, Kumar N, Murti K (2024) Impact of fluorosis on molecular predictors in pathogenesis of type 2 diabetes associated microvascular complications. J Trace Elem Med Biol 86:127506. https:\/\/doi.org\/10.1016\/j.jtemb.2024.127506","journal-title":"J Trace Elem Med Biol"},{"key":"10670_CR33","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200845R","author":"S Mei","year":"2022","unstructured":"Mei S, Li L, Zhou X, Xue C, Livingston MJ, Wei Q, Dai B, Mao Z, Mei C, Dong Z (2022) Susceptibility of renal fibrosis in diabetes: role of hypoxia inducible factor\u20101. FASEB J. https:\/\/doi.org\/10.1096\/fj.202200845R","journal-title":"FASEB J"},{"issue":"2","key":"10670_CR34","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.toxlet.2009.07.014","volume":"190","author":"A Mendoza-Schulz","year":"2009","unstructured":"Mendoza-Schulz A, Solano-Agama C, Arreola-Mendoza L, Reyes-M\u00e1rquez 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(2):179\u2013186. https:\/\/doi.org\/10.1016\/j.toxlet.2009.07.014","journal-title":"Toxicol Lett"},{"issue":"6","key":"10670_CR35","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.semnephrol.2007.09.003","volume":"27","author":"ML Merchant","year":"2007","unstructured":"Merchant ML, Klein JB (2007) Proteomics and diabetic nephropathy. Semin Nephrol 27(6):627\u2013636. https:\/\/doi.org\/10.1016\/j.semnephrol.2007.09.003","journal-title":"Semin Nephrol"},{"issue":"6","key":"10670_CR36","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.3390\/ijms11062443","volume":"11","author":"JA Morales-Gonz\u00e1lez","year":"2010","unstructured":"Morales-Gonz\u00e1lez JA, Guti\u00e9rrez-Salinas J, Garc\u00eda-Ortiz L, Del Carmen Chima-Gal\u00e1n M, Madrigal-Santill\u00e1n E, Esquivel-Soto J, Esquivel-Chirino C, Garc\u00eda-Luna Y Gonz\u00e1lez-Rubio M (2010) Effect of sodium fluoride ingestion on malondialdehyde concentration and the activity of antioxidant enzymes in rat erythrocytes. Int J Mol Sci 11(6):2443\u20132452. https:\/\/doi.org\/10.3390\/ijms11062443","journal-title":"Int J Mol Sci"},{"issue":"10","key":"10670_CR37","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1177\/154405910508401009","volume":"84","author":"S Otsuki","year":"2005","unstructured":"Otsuki S, Morshed SRM, Chowdhury SA, Takayama F, Satoh T, Hashimoto K, Sugiyama K, Amano O, Yasui T, Yokote Y, Akahane K, Sakagami H (2005) Possible link between glycolysis and apoptosis induced by sodium fluoride. J Dent Res 84(10):919\u2013923. https:\/\/doi.org\/10.1177\/154405910508401009","journal-title":"J Dent Res"},{"key":"10670_CR38","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.taap.2018.09.010","volume":"358","author":"HABDS Pereira","year":"2018","unstructured":"Pereira HABDS, Dionizio AS, Araujo TT, Fernandes MDS, Iano FG, Buzalaf MAR (2018) Proposed mechanism for understanding the dose- and time-dependency of the effects of fluoride in the liver. Toxicol Appl Pharmacol 358:68\u201375. https:\/\/doi.org\/10.1016\/j.taap.2018.09.010","journal-title":"Toxicol Appl Pharmacol"},{"issue":"9","key":"10670_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075343","volume":"8","author":"HABDS Pereira","year":"2013","unstructured":"Pereira HABDS, Leite ADL, Charone S, Lobo JGVM, Cestari TM, Peres-Buzalaf C, Buzalaf MAR (2013) Proteomic analysis of liver in rats chronically exposed to fluoride. PLoS ONE 8(9):e75343. https:\/\/doi.org\/10.1371\/journal.pone.0075343","journal-title":"PLoS ONE"},{"key":"10670_CR40","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.biochi.2017.02.004","volume":"135","author":"GB Peres","year":"2017","unstructured":"Peres GB, Schor N, Michelacci YM (2017) Impact of high glucose and AGEs on cultured kidney-derived cells. Effects on cell viability, lysosomal enzymes and effectors of cell signaling pathways. Biochimie 135:137\u2013148. https:\/\/doi.org\/10.1016\/j.biochi.2017.02.004","journal-title":"Biochimie"},{"key":"10670_CR41","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.11883","author":"DA Ribeiro","year":"2017","unstructured":"Ribeiro DA, Cardoso CM, Yujra VQ (2017) Fluoride induces apoptosis in mammalian cells: in vitro and in vivo studies. Anticancer Res. https:\/\/doi.org\/10.21873\/anticanres.11883","journal-title":"Anticancer Res"},{"key":"10670_CR42","doi-asserted-by":"publisher","DOI":"10.3389\/froh.2022.916372","volume":"3","author":"H Saad","year":"2022","unstructured":"Saad H, Escoube R, Babajko S, Houari S (2022) Fluoride intake through dental care products: a systematic review. Frontiers in Oral Health 3:916372. https:\/\/doi.org\/10.3389\/froh.2022.916372","journal-title":"Frontiers in Oral Health"},{"issue":"8","key":"10670_CR43","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1080\/15376516.2021.1938325","volume":"31","author":"MR Santesso","year":"2021","unstructured":"Santesso MR, Oliveira FA, Tokuhara CK, Oliveira GSN, Levy FM, Antonio LS, Buzalaf MAR, Oliveira RC (2021) Fluoride effects on cell viability and ENaC expression in kidney epithelial cells. Toxicol Mech Methods 31(8):566\u2013571. https:\/\/doi.org\/10.1080\/15376516.2021.1938325","journal-title":"Toxicol Mech Methods"},{"issue":"2\u20133","key":"10670_CR44","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.tox.2004.06.058","volume":"204","author":"D Shanthakumari","year":"2004","unstructured":"Shanthakumari D, Srinivasalu S, Subramanian S (2004) Effect of fluoride intoxication on lipidperoxidation and antioxidant status in experimental rats. Toxicology 204(2\u20133):219\u2013228. https:\/\/doi.org\/10.1016\/j.tox.2004.06.058","journal-title":"Toxicology"},{"key":"10670_CR45","doi-asserted-by":"publisher","unstructured":"Siddiqi NJ (2012) Studies on the comparative effect of sodium fluoride on collagen content in various rat organs. African Journal of Biotechnology, 11(55). https:\/\/doi.org\/10.5897\/AJB11.1707","DOI":"10.5897\/AJB11.1707"},{"key":"10670_CR46","unstructured":"Srinivasan K, Ramarao P (2004) Animal models in type 2 diabetes research: An overview."},{"issue":"9","key":"10670_CR47","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1007\/BF00400357","volume":"36","author":"Trivedi N, Mithal A, Gupta SK, Godbole MM, The Fluoride Collaborative Study Group","year":"1993","unstructured":"Trivedi N, Mithal A, Gupta SK, Godbole MM, The Fluoride Collaborative Study Group (1993) Reversible impairment of glucose tolerance in patients with endemic fluorosis. Diabetologia 36(9):826\u2013828. https:\/\/doi.org\/10.1007\/BF00400357","journal-title":"Diabetologia"},{"issue":"1\u20133","key":"10670_CR48","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s12011-014-0148-8","volume":"162","author":"Y Wei","year":"2014","unstructured":"Wei Y, Wu Y, Zeng B, Zhang H (2014) Effects of sodium fluoride treatment in vitro on cell proliferation, BMP-2 and BMP-3 expression in human osteosarcoma MG-63 cells. Biol Trace Elem Res 162(1\u20133):18\u201325. https:\/\/doi.org\/10.1007\/s12011-014-0148-8","journal-title":"Biol Trace Elem Res"},{"issue":"6","key":"10670_CR49","doi-asserted-by":"publisher","first-page":"2679","DOI":"10.1093\/advances\/nmac050","volume":"13","author":"FV Zohoori","year":"2022","unstructured":"Zohoori FV, Buzalaf M (2022) Fluoride. Adv Nutr 13(6):2679\u20132680. https:\/\/doi.org\/10.1093\/advances\/nmac050","journal-title":"Adv Nutr"}],"container-title":["Journal of Molecular Histology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-025-10670-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-025-10670-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-025-10670-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:24:45Z","timestamp":1772000685000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10735-025-10670-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10670"],"URL":"https:\/\/doi.org\/10.1007\/s10735-025-10670-6","relation":{},"ISSN":["1567-2379","1567-2387"],"issn-type":[{"value":"1567-2379","type":"print"},{"value":"1567-2387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"42"}}