Neuroprotective Effects of Boric Acid against Fluoride Toxicity on Rat Synaptosomes

Abstract

Objective: Fluoride toxicity primarily contributes to the production of reactive oxygen and nitrogen derivatives, trigger the cell death pathways by causing lipid peroxidation and DNA damage. Boric acid (BA) contributes to preservation of membrane integrity and function and maintenance of redox balance due to its high affinity to some metabolites in the organism. The aim of this study was to investigate the protective effect of BA on neurodegenerative processes against the toxic effects of sodium fluoride (NaF) administered at different doses on rat brain synaptosomes.

Material and Methods: Synaptosomes obtained from the rat frontal cortex were administered at different doses of sodium fluoride (NaF) to determine the most toxic dose of NaF. Determined toxic dose of NaF for synaptosomes and BA concentrations were administered in vitro at 37°C for 30min and then the parameters of malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, Na/K ATPase activity and DNA fragmentation value were measured spectrophotometrically.

Results: There was a statistically significant difference between measured parameters, when the 80mg/L NaF group was compared with the control group. We found that 10 and 25 mM BA treatment provided a significant improvement in MDA, SOD, Na/K ATPase and DNA fragmentation compared to the 80mg/L NaF group. The 5 mM BA concentration was not found effective dose according to other doses.

Conclusion: In conclusion, BA has potential for neuroprotective effects against cellular damage caused by NaF.  The results suggest that the BA can be a neuroprotective therapeutic agent for fluoride toxicity.

Keywords

• Boric acid,Neuroprotection,Synaptosomes,Sodium fluoride,Oxidative stress

Kaynakça

1. 1. Hassan HA, Yousef MI. Mitigating effects of antioxidant properties of black berry juice on sodium fluoride induced hepatotoxicity and oxidative stress in rats. Food Chem Toxicol. 2009;47:2332-2337.
2. 2. Whitford GM, Bawden JW, Bowen WH, Brown LJ, Ciardi JE, Clarkson TW, et al. Report for Working Group I: strategies for improving the assessment of fluoride accumulation in body fluids and tissues. Adv Dent Res. 1994;8:113-115.
3. 3. Domingo JL. Health risk of dietary exposure to perfluorinated compounds. Environ Int. 2012;40:187-195.
4. 4. Urbansky ET. Fate of fluorosilicate drinking water additives. Chem Rev. 2002;102:2837-2854.
5. 5. Basha PM, Rai P, Begum S. Evaluation of fluoride-induced oxidative stress rat brain: a multigeneration study. Biol Trace Elem Res. 2011;142:623-637.
6. 6. Bharti VK, Srivastava RS. Fluoride-induced oxidative stress in rat’s brain and its amelioration by buffalo (bubalus bubalis) pineal proteins and melatonin. Biol Trace Elem Res. 2009;130:131-140.
7. 7. Shanthakumari D, Srinivasalu S, Subramanian S. Effect of fluoride intoxication on lipid peroxidation and antioxidant status in experimental rats. Toxicol. 2004;204:219-228.
8. 8. Tiwari H, Rao MV. Curcumin supplementation protects from genotoxic effects of arsenic and fluoride. Food Chem Toxicol. 2010;48:1234-1238.

9. 9. Reddy VD, Padmavathi P, Bulle S, Hebbani AV, Marthadu SB, Venugopalacharyulu NC, et al. Association between alcohol-induced oxidative stress and membrane properties in synaptosomes: A protective role of vitamin E. Neurotoxicol Teratol. 2017;63:60-65.
10. 10. Gray EG, Burgoyne RD, Westrum LE, Cumming R, Barron J. The enigma of microtubule coils in brain synaptosomes. Proc R Soc Lond B Biol Sci. 1982;216(1205):385-96.
11. 11. Whittaker VP, Michaleson IA, Jeanette R. The separation of synaptic vesicles from nerve-ending particles (synaptosomes). Biochem J. 1964;90(2):293-303.
12. 12. Nielsen FH. Is boron nutritionally relevant? Nutr Rev 2008;66:183‑191.
13. 13. Hunt CD. Boron. In Encyclopedia of Dietary Supplements. 1st edition. Coates PM, Blackman MR, Cragg GM, Levine M, Moss J and White JD (eds). Marcel Dekker, New York, NY, 2005, pp55‑65.
14. 14. Altieri S, Bortolussi S, Bruschi P, Chiari P, Fossati F, Stella S, Prati U, Roveda L, Zonta A, Zonta C, Ferrari C, Clerici A, Nano R, Pinelli T. Neutron autoradiography imaging of selective boron uptake in human metastatic tumours. Appl Radiat Isot 2008; 66:1850‑1855.
15. 15. Hunt CD, Idso JP. Dietary boron as a physiological regulatör of the normal inflammatory response: A review and current research progress. J Trace Elem Exp Med 1999;12:221‑233.
16. 16. Ince S, Keles H, Erdogan M, Hazman O, Kucukkurt I. Protective effect of boric acid against carbon tetrachloride‑induced hepatotoxicity in mice. Drug Chem Toxicol 2012;35:285‑292.
17. 17. Sogut I, Oglakci A, Kartkaya K, Ol KK, Sogut MS, Kanbak G, Inal ME. Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome. Exp Ther Med 2015;9(3):1023-7.
18. 18. Whittaker VP, Michaleson IA, Jeanette R. The separation of synaptic vesicles from nerve-ending particles (synaptosomes). The Biochem J. 1964;90:293-303.
19. 19. Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J of Bio Chem. 1949;177:751-766.
20. 20. Okhawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-358.
21. 21. Sun Y, Oberlet LW, Li Y. A Simple Method for Clinical Assay of Superoxide Dismutase. Clin. Chem. 1988;34:497-500.
22. 22. Durmaz R, Ertilav K, Akyüz F, Kanbak G, Bildirici K, Tel E. Lazaroid U-74389G attenuates edema in rat brain subjected to post-ischemic reperfusion injury. J Neurol Sci. 2003;215:87-93.
23. 23. Atroshi F, Rizzo A, Biese I, Veijalainen P, Saloniemi H, Sankari S, Andersson K. Fumonisin B1-induced DNA damage in rat liver and spleen: effect of pretreatment with coenzyme Q10, L-carnitine, a-tocopherol and selenium. Pharmacol Res. 1999;40:459-467.
25. 24. Zhang M, Wang A, He W, He P, Xu B, Xia T, Chen X, Yang K. Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in primary cultured hippocampal neurons. Toxicol. 2007;236:208-216.
26. 25. Izquierdo-Vega JA, Sánchez-Gutiérrez M, Del Razo LM. Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss. Toxicol Appl Pharmacol. 2008;230(3):352-7.
27. 26. Borges CG, Canani CR, Fernandes CG, Zanatta Â, Seminotti B, Ribeiro CA, Leipnitz G, Vargas CR, Wajner M. Reactive nitrogen species mediate oxidative stress and astrogliosis provoked by in vivo administration of phytanic acid in cerebellum of adolescent rats: a potential contributing pathomechanism of cerebellar injury in peroxisomal disorders. Neuroscience 2015;304:122-32.
28. 27. Kaur T, Bijaria RK, Nehru B. Effect of concurrent chronic exposureof fluoride and aluminium on rat brain. Drug and Chem Toxicol. 2009;32:215-221.
29. 28. Feng P, Wei J, Zhang Z. Influence of selenium and fluoride on blood antioxidant capacity of rats. Exp Toxicol Pathol. 2012;64:565-568.
30. 29. Alirezaei M, Khoshdel Z, Dezfoulian O, Rashidipour M, Taghadosi V. Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats. J Physiol Sci. 2015;65:243-52.
31. 30. Büyükgüzel E, Büyükgüzel K, Snela M, Erdem M, Radtke K, Ziemnicki K, Adamski Z. Effect of boric acid on antioxidant enzyme activity, lipid peroxidation, and ultrastructure of midgut and fat body of Galleria mellonella. Cell Biol Toxicol. 2013;29:117-29.
52. 31. Kucukkurt I, Ince S, Demirel HH, Turkmen R, Akbel E, Celik Y. The Effects of Boron on Arsenic-Induced Lipid Peroxidation and Antioxidant Status in Male and Female Rats. J Biochem Mol Toxicol. 2015;29(12):564-71.
53. 32. Barbier O, Arreola-Mendoza L, Del Razo LM. Molecular mechanisms of fluoride toxicity. Chem Biol Interact. 2010;188(2):319-33.
54. 33. Adamek E, Pawłowska-Goral K, Bober K. In vitro and in vivo effects of fluoride ions on enzyme activity. Ann Acad Med Stetin. 2005;51:69-85.
55. 34. Kravtsova VV, Kravtsov OV. Inactivation of Na+/K+-ATPase from cattle brain by sodium fluoride. Ukr Biokhim Zh. 2004;76:39-47.
56. 35. Sinha S, Ghosh M, Mukherjee A. Evaluation of multi-endpoint assay todetect genotoxicity and oxidative stress in mice exposed to sodium fluoride. Mutat Res. 2013;751:59-65.
57. 36. He LF, Chen JG. DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes. World J Gastroenterol. 2006;7:1144-1148.
58. 37. Song GH, Wang RL, Chen ZY, Zhang B, Wang HL, Liu ML, Gao JP, Yan XY. Toxic effects of sodium fluoride on cell proliferation and apoptosis of Leydig cells from young mice. J Physiol Biochem. 2014;70:761-768.
59. 38. Zhang M, Wang A, Xia T, He P. Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-kappaB in primary cultured rat hippocampal neurons. Toxicol Lett. 2008;179(1):1-5.