Fluoride Action Network

Abstract

The objective of this study was to determine the effect of fluoride (F) and arsenic (As) on the activity of acetylcholinesterase (AChE), a critically important nervous system enzyme, and to test the protective role of buffalo epiphyseal (pineal) proteins (BEP) in rats. Arsenic (20 mg/kg BW, intraperitoneally) and F (150 ppm, perorally) were exposed, and BEP was administered intraperitoneally (100 ? g/kg BW) along with F and As to rats for 7 days. As and F exposure significantly (p < 0.05) increased their levels in plasma and decreased the activity of AChE in plasma, RBCs, heart, and brain of rats. Interestingly, As- and F-induced inhibition of AChE activities increased As and F levels in plasma, and organs were significantly (p < 0.05) counteracted by BEP administration. These findings indicate the protective role of buffalo (Bubalus bubalis) epiphyseal proteins on F- and As-induced adverse changes in AChE activity as a candidate biomarker for neurotoxicity in female rats.


*Original abstract online at https://onlinelibrary.wiley.com/doi/10.1002/jbt.20407


  1. 1.

    Varner JA, Jensen KF, Horvath W, Isaacson RL (1998) Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity. Brain Res 784:284–298

    PubMed  Article  CAS  Google Scholar

  2. 2.

    Mullenix PJ, Denbesten PK, Schunior A, Kernan WJ (1995) Neurotoxicity of sodium fluoride in rats. Neurotoxicol Teratol 17:169–177

    PubMed  Article  CAS  Google Scholar

  3. 3.

    Shashi A (1992) Studies on alterations in brain lipid metabolism following experimental fluorosis. Fluoride 25:77–84

    CAS  Google Scholar

  4. 4.

    Shashi A, Singh JP, Thapar SP (1994) Effect of long-term administration of fluoride on levels of proteins, free amino acids and RNA in rabbit brain. Fluoride 27:155–159

    CAS  Google Scholar

  5. 5.

    Vani ML, Reddy KP (2000) Effects of fluoride accumulation on some enzymes of brain and gastrocnemius muscle of mice. Fluoride 33:17–26

    CAS  Google Scholar

  6. 6.

    He H, Chen ZS, Liu XM (1989) The influence of fluoride on human embryo. Chin J Ctrl Endem Dis 4:136–137

    Google Scholar

  7. 7.

    Xiang Q, Liang Y, Chen L, Wang C, Chen B, Chen X (2003) Effect of fluoride in drinking water on children’s intelligence. Fluoride 36:84–94

    CAS  Google Scholar

  8. 8.

    Nunez J, Couchie D, Aniello F, Bridoux AM (1991) Regulation by thyroid hormone of microtubule assembly and neuronal differentiation. Neurochem Res 16:975–982

    PubMed  Article  CAS  Google Scholar

  9. 9.

    Thompson CC, Potter GB (2000) Thyroid hormone action in neural development. Cereb Cortex 10:939–945

    PubMed  Article  CAS  Google Scholar

  10. 10.

    Anderson GW (2001) Thyroid hormones and the brain. Front Neuroendocrinol 22:1–17

    PubMed  Article  CAS  Google Scholar

  11. 11.

    Bernal J (2002) Action of thyroid hormone in brain. J Endocrinol Invest 25:268–288

    PubMed  CAS  Google Scholar

  12. 12.

    Guan ZZ (1986) Morphology of the brain of the offspring of rats with chronic fluorosis. Zhonghua Bing Li Xue Za Zhi 15:297–299

    PubMed  CAS  Google Scholar

  13. 13.

    Lu Y, Sun ZR, Wu LN, Wang X, Lu W, Liu SS (2000) Study of cognitive function impairment caused by fluorosis. Fluoride 33:74–78

    CAS  Google Scholar

  14. 14.

    Trivedi MH, Verma RJCN, Patel RS, Sathawara NG (2007) Effect of high fluoride water on children’s intelligence in India. Fluoride 40:178–183

    Google Scholar

  15. 15.

    Niu RY, Sun ZL, Wang JM, Cheng Z, Wang JD (2008) Effects of fluoride and lead on locomotor behavior and expression of Nissl body in brain of adult rats. Fluoride 41:276–282

    CAS  Google Scholar

  16. 16.

    Wu CX, Gu XL, Ge YM, Zhang JH, Wang JD (2006) Effects of high fluoride and arsenic on brain biochemical indexes and learning-memory in rats. Fluoride 39:274–279

    CAS  Google Scholar

  17. 17.

    Parveen M, Kumar S (2002) Acetylcholinesterase enzyme: a tool for monitoring environmental toxicity in mammals. In: Modern trends in environmental biology. CBS Publishers, New Delhi pp 307–323

  18. 18.

    Collins TF, Sprando RL, Black TN, Shackelford ME, Bryant MA, Olejnik N, Ames MJ, Rorie JI, Ruggles DI (2001) Multigenerational evaluation of sodium fluoride in rats. Food Chem Toxicol 39:601–613

    PubMed  Article  CAS  Google Scholar

  19. 19.

    CollinsTF SRL, Black TN, Shackelford ME, Olejnik N, Ames MJ, Rorie JI, Ruggles DI (2001) Developmental toxicity of sodium fluoride measured during multiple generations. Food Chem Toxicol 39:867–876

    Article  Google Scholar

  20. 20.

    Cicek E, Aydin G, Akdogan M, Okutan H (2005) Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats. Hum Exp Toxicol 24:79–87

    PubMed  Article  CAS  Google Scholar

  21. 21.

    Aydin G, Cicek E, Akdogan M, Gokalp O (2003) Histopathological and biochemical changes in lung tissues of rats following administration of fluoride over several generations. J Appl Toxicol 23:437–446

    PubMed  Article  CAS  Google Scholar

  22. 22.

    Karaoz E, Oncu M, Gulle K, Kanter M, Gultekin F, Karaoz S, Mumcu E (2004) Effect of chronic fluorosis on lipid peroxidation and histology of kidney tissues in first- and second-generation rats. Biol Trace Elem Res 102:199–208

    PubMed  Article  CAS  Google Scholar

  23. 23.

    Meral O, Ahmet K, Erdal K, Hakan D, Emin S, Fatih G (2007) Effect of long-term fluoride exposure on lipid preoxidation and histology of testes in first and second generation rats. Biol Trace Elem Res 118:260–268

    Article  Google Scholar

  24. 24.

    Thomas JA (1996) Endocrine methods. Academic, New York, pp 157–186

    Google Scholar

  25. 25.

    Ellman GL, Courtney KD, Andres VJR, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    PubMed  Article  CAS  Google Scholar

  26. 26.

    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar

  27. 27.

    Inkielewicz I, Czarnowski W, Krechniak J (2003) Determination of fluoride in soft tissues. Fluoride 36:16–20

    CAS  Google Scholar

  28. 28.

    Bures J, Buresova O, Huston JP (1983) Techniques and basic experiments for the study of brain and behaviour. Elsevier, Amsterdam

    Google Scholar

  29. 29.

    Madan J, Puri JP, Singh JK (2009) Growth, feed efficiency and blood profile of buffalo calves consuming high levels of fluoride. Trop Anim Heal Prod 41:295–298

    Article  Google Scholar

  30. 30.

    Zhan XA, Li JX, Wang M, Xu ZR (2006) Effects of fluoride on growth and thyroid function in young pigs. Fluoride 39:95–100

    CAS  Google Scholar

  31. 31.

    Trabelsi M, Guermazi F, Zeghal N (2001) Effect of fluoride on thyroid function and cerebellar development in mice. Fluoride 34:165–173

    CAS  Google Scholar

  32. 32.

    Wu C, Gu X, Wu Y, Wang J (2008) Effects of fluoride and arsenic on serum thyroid hormone in rats. Journal of Herbal Medicine and Toxicology 2:39–43

    CAS  Google Scholar

  33. 33.

    Das K, Chainy GB (2004) Thyroid hormone influences antioxidant defense system in adult rat brain. Neurochem Res 29:1755–1766

    PubMed  Article  CAS  Google Scholar

  34. 34.

    Basha PM, Rai P, Begum S (2011) Evaluation of fluoride-induced oxidative stress in rat brain: a multigeneration study. Biol Trace Elem Res doi:10.1007/s12011-010-8780-4

  35. 35.

    Gao Q, Liu YJ, Guan ZZ (2009) Decreased learning and memory ability in rats with fluorosis: increased oxidative stress and reduced cholinesterase activity in the brain. Fluoride 42:277–285

    CAS  Google Scholar

  36. 36.

    Pereira M, Dombrowski PA, Losso EM, Chioca LR, Cunha CD, Andreatini R (2011) Memory impairment induced by sodium fluoride is associated with changes in brain monoamine levels. Neurotox Res 19:55–62. doi:10.1007/s12640-009-9139-5

    PubMed  Article  CAS  Google Scholar

  37. 37.

    El Lethey HS, Kamel MM, Shaheed IB (2010) Neurobehavioral toxicity produced by sodium fluoride in drinking water of laboratory rats. Journal of American Science 6(5):54–63

    Google Scholar

  38. 38.

    Thiel C, Huston J, Schwarting R (1998) Hippocampal acetylcholine and habituation learning. Neuroscience 85:1253–1262

    PubMed  Article  CAS  Google Scholar

  39. 39.

    Leussis M, Bolivar V (2006) Habituation in rodents: a review of behaviour, neurobiology and genetics. Neurosci Biobehav Rev 30:1045–1064

    PubMed  Article  Google Scholar

  40. 40.

    Thiel C, Müller C, Huston J, Schwarting R (1999) High versus low reactivity to a novel environment: behavioural pharmacology and neurochemical assessments. Neurosci 93:243–251

    Article  CAS  Google Scholar

  41. 41.

    Long Y, Wang Y, Chen J, Jiang S, Nordberg A, Guan Z (2002) Decreased number of nicotinic acetylcholine receptors in the brain of rats with chronic fluorosis. Neurotoxicol Teratol 24:751–757

    PubMed  Article  CAS  Google Scholar

  42. 42.

    Wang JD, Ge YM, Ning HM, Wang SL (2004) Effects of high fluoride and low iodine on biochemical indexes of the brain and learning-memory of offspring rats. Fluoride 37:201–208

    CAS  Google Scholar

  43. 43.

    Bhatnagar M, Rao P, Saxena A, Bhatnagar R, Meena P, Barbar S, Chouhan A, Vimal S (2006) Biochemical changes in brain and other tissues of young adult female mice from fluoride in their drinking water. Fluoride 39:280–284

    CAS  Google Scholar

  44. 44.

    Zhai JX, Guo ZY, Hu CL, Wang QN, Zhu QX (2003) Studies on fluoride concentration and cholinesterase activity in rat hippocampus. Chin J Ind Hyg Occup Dis 21:102–104

    CAS  Google Scholar

  45. 45.

    Wen XP, Sang ZP, Chen YX (1998) The effect of fluoride on ChE and acetylcholine. Chin J Endemiol 17:56–57

    Google Scholar

  46. 46.

    Chinoy NJ, Memon MR (2001) Beneficial effects of some vitamins and calcium on fluoride and aluminium toxicity on gastrocnemius muscle and liver of male mice. Fluoride 34:21–33

    CAS  Google Scholar

  47. 47.

    Blaylock RL (2004) Excitotoxicity: a possible central mechanism in fluoride neurotoxicity. Fluoride 37:301–314

    CAS  Google Scholar

  48. 48.

    Blaylock RL (2007) Fluoride neurotoxicity and excitotoxicity/microglial activation: critical need for more research. Fluoride 40:89–92

    CAS  Google Scholar

  49. 49.

    Goodlett CR, Hamre KM, West JR (1992) Dissociation of spatial navigation and visual guidance performance in Purkinje cell degeneration (pcd) mutant mice. Behav Brain Res 47:129–141

    PubMed  Article  CAS  Google Scholar

  50. 50.

    Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Invest 111:785–793

    PubMed  CAS  Google Scholar

  51. 51.

    Shivarajashankara YM, Shivashankara AR, Bhat PG, Rao SM, Rao SH (2002) Histological changes in the brain of young fluoride-intoxicated rats. Fluoride 35:12–21

    CAS  Google Scholar

Download references