Fluoride Action Network

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Abstract

Sodium fluoride (NaF) is used in water fluoridation and dental products such as mouth rinses and toothpastes. Resveratrol is a natural polyphenol with antioxidant and anti-inflammatory properties. The present study was carried out to evaluate the toxicity of NaF and the protective role of resveratrol in Drosophila melanogaster. For longevity assay, Harwich strain of D. melanogaster was treated with NaF (0, 10, 30, 50, 70 and 90 mg/kg diet) throughout the lifespan and daily mortality recorded. Then, flies were again treated with similar doses of NaF for seven days to evaluate survival rate and oxidative stress markers. Thereafter, 60 mg resveratrol/kg diet was selected to determine its ameliorative role in NaF (70 mg/kg)-induced toxicity in flies: Group A (control), Group B (60 mg resveratrol/kg diet), Group C (70 mg NaF/kg diet), and Group D (resveratrol, 60 mg/kg diet) + NaF, 70 mg/kg diet). Thereafter, Glutathione-S-transferase (GST), catalase and acetylcholinesterase (AchE) activities, as well as total thiol (T-SH), nitrites/nitrates and hydrogen peroxide (H2O2) levels were determined. The results showed that resveratrol prevented NaF-induced elevation of H2O2 and nitrites/nitrates levels, as well as catalase activity. In addition, resveratrol restored NaF-induced inhibition of GST and AChE activities and depletion of T-SH content (P < 0.05). Conclusively, resveratrol offered protective benefit against NaF-mediated toxicity in flies due to its antioxidant and anti-inflammatory properties.

Impact statement: D. melanogaster was used to understand the impact of NaF on lifespan and emergence rate as well as the rescue role of resveratrol. These parameters are difficult to carry out in previously used models such as rodents. This further enforces in part, the suitability of D. melanogaster in studying NaF-induced toxicity and the therapeutic effects of drugs.

Additionally, we found that resveratrol rescued D. melanogaster from oxidative stress-induced by sodium fluoride (NaF) administration. This study is of public health significance as it indicated that the consumption of fruits rich in resveratrol such as grapes may offer protective role against inadvertent exposure to NaF and related chemicals.

Keywords: Drosophila melanogaster; antioxidants; oxidative stress; resveratrol; sodium fluoride.

*Original abstract online at https://journals.sagepub.com/doi/10.1177/1535370219890334

References

1. Ozsvath, DL. Fluoride and environmental health: a review. Rev Environ Sci Biotechnol 2009; 8:59–79
Google Scholar | Crossref
2. USNRC. Health effects of ingested fluoride. Washington D.C.: National Research Council, National Academy Press, 1993
Google Scholar
3. Zuo, H, Chen, L, Kong, M, Qiu, L, Lü, P, Wu, P, Yang, Y, Chen, K. Toxic effects of fluoride on organisms. Life Sci 2018; 198:18–24
Google Scholar | Crossref | Medline
4. Chouhan, S, Flora, SJ. Effects of fluoride on the tissue oxidative stress and apoptosis in rats: biochemical assays supported by IR spectroscopy data. Toxicology 2008; 254: 61–7
Google Scholar | Crossref | Medline | ISI
5. Pastor, RF, Restani, P, Di Lorenzo, C, Orgiu, F, Teissedre, PL, Stockley, C, Ruf, JC, Quini, CI, GarcìaTejedor, N, Gargantini, R, Aruani, C, Prieto, S, Murgo, M, Videla, R, Penissi, A, Iermoli, RH. Resveratrol, human health and winemaking perspectives. Crit Rev Food Sci Nutr 2019; 59:1237–55
Google Scholar | Crossref | Medline
6. Burns, J, Yokota, T, Ashihara, H, Lean, ME, Crozier, A. Plant foods and herbal sources of resveratrol. J Agric Food Chem 2002; 50:3337–40
Google Scholar | Crossref | Medline | ISI
7. Yeh, CB, Hsieh, MJ, Lin, CW, Chiou, HL, Lin, PY, Chen, TY, Yang, SF. The antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by SP-1 modulation. PLoS One 2013; 8:e56661
Google Scholar | Crossref | Medline
8. Abolaji, AO, Adedara, AO, Adie, MA, Vicente-Crespo, M, Farombi, EO. Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster. Biochem Biophys Res Commun 2018; 503: 1042–8
Google Scholar | Crossref | Medline
9. Howitz, KT, Bitterman, KJ, Cohen, HY, Lamming, DW, Lavu, S, Wood, JG. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003; 425:191–6
Google Scholar | Crossref | Medline | ISI
10. Baur, JA, Pearson, KJ, Price, NL, Jamieson, NL, Lerin, C, Kalra, A. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444:337–42
Google Scholar | Crossref | Medline | ISI
11. Bier, E. Drosophila, the golden bug, emerges as a tool for human genetics. Nat Rev Genet 2005; 6:9–23
Google Scholar | Crossref | Medline
12. Adedara, IA, Klimaczewski, CV, Barbosa, NB, Farombi, EO, Souza, DO, Rocha, JB. Influence of diphenyl diselenide on chlorpyrifos-induced toxicity in Drosophila melanogaster. J Trace Elem Med Biol 2015; 32:52–9
Google Scholar | Crossref | Medline
13. Benford, DJ, Hanley, AB, Bottrill, K, Oehlschlager, S, Balls, M, Brance, F, Castegnara, JJ, Descotes, J, Hemminiky, K, Lindsay, D, Schilter, B. Biomarkers as predictive tools in toxicity testing: the report and recommendations of ECVAM workshop 40. Altern Lab Anim 2000; 28:119–31
Google Scholar | SAGE Journals
14. Atmaca, N, Atmaca, HT, Kanici, A, Anteplioglu, T. Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity in rats. Food Chem Toxicol 2014; 70:191–7
Google Scholar | Crossref | Medline
15. Pal, S, Sarkar, C. Protective effect of resveratrol on fluoride induced alteration in protein and nucleic acid metabolism, DNA damage and biogenic amines in rat brain. Environ Toxicol Pharmacol 2014; 38:684–99
Google Scholar | Crossref | Medline
16. Sharma, C, Suhalka, P, Bhatnagar, M. Curcumin and resveratrol rescue cortical-hippocampal system from chronic fluoride-induced neurodegeneration and enhance memory retrieval. Int J Neurosci 2018; 13:1–15
Google Scholar
17. Feany, MB, Bender, WW. A drosophila model of Parkinson’s disease. Nature 2000; 404:394–8
Google Scholar | Crossref | Medline | ISI
18. Farombi, EO, Abolaji, AO, Farombi, TH, Oropo, AS, Owoje, OA, Awunah, MT. Garcina kola seeds biflavonoid fraction (kolaviron), increases longevity and attenuates rotenone induced toxicity in Drosophila melanogaster. Pestic Biochem Physiol 2018; 145:39–45
Google Scholar | Crossref | Medline
19. Lowry, OH, Rosebrough, NJ, Farr, AL, Randall, RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193:265–75
Google Scholar | Crossref | Medline | ISI
20. Ellman, GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82:70–7
Google Scholar | Crossref | Medline | ISI
21. Habig, WH, Jakoby, WB. Assays for differentiation of glutathione-S-transferases. Meth Enzymol 1981; 77:398–405
Google Scholar | Crossref | Medline
22. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-126
Google Scholar
23. Ellman, GL, Courtney, KD, Andres, V, Feathers-Stone, RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7:88–95
Google Scholar | Crossref | Medline | ISI
24. Wolff, SP. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Meth Enzymol 1994; 233:182–9
Google Scholar | Crossref | ISI
25. Eleftherianos, I, More, K, Spivack, S, Paulin, E, Khojandi, A, Shukla, S. Nitric oxide levels regulate the immune response of Drosophila melanogaster reference laboratory strains to bacterial infections. Infect Immun 2014; 82:69–81
Google Scholar | Crossref
26. Song, C, Zhao, J, Fu, B, Li, D, Mao, T, Peng, W, Wu, H, Zhang, Y. Melatonin-mediated upregulation of Sirt3 attenuates sodium fluoride-induced hepatotoxicity by activating the MT1-PI3K/AKT-PGC-1? signaling pathway. Free Radic Biol Med 2017; 112:616–30
Google Scholar | Crossref | Medline
27. Ameeramja, J, Panneerselvam, L, Govindarajan, V, Jeyachandran, S, Baskaralingam, V, Perumal, E. Tamarind seed coat ameliorates fluoride induced cytotoxicity, oxidative stress, mitochondrial dysfunction and apoptosis in A549 cells. J Hazard Mater 2016; 301:554–65
Google Scholar | Crossref | Medline
28. Hamza, RZ, Nahla, S, El-Shenawy , Ismail, HAA. Protective effects of blackberry and quercetin on sodium fluoride-induced oxidative stress and histological changes in the hepatic, renal, testis and brain tissue of male rat. J Basic Clin Phys Pharm 2014; 26:3
Google Scholar
29. Miranda, GHN, Gomes, BAQ, Bittencourt, LO, Aragão, WAB, Nogueira, LS, Dionizio, AS, Buzalaf, MAR, Monteiro, MC, Lima, RR. Chronic exposure to sodium fluoride triggers oxidative biochemistry misbalance in mice: effects on peripheral blood circulation. Oxid Med Cell Longev 2018; 2018:8379123
Google Scholar | Crossref | Medline
30. Zhou, Y, Zhang, H, He, J, Chen, X, Ding, Y, Wang, Y, Liu, X. Effects of sodium fluoride on reproductive function in female rats. Food Chem Toxicol 2013; 56:297–303
Google Scholar | Crossref | Medline
31. Chioca, LR, Müller, JC, Boareto, AC, Andreatini, R, Dalsenter, PR. Sodium fluoride does not alter sperm production or sperm morphology in rats. Braz Arch Biol Technol 2012; 55:257–262
Google Scholar | Crossref
32. Charpentier, A, Fournie, D. Levels of total acetylcholinesterase in Drosophila melanogaster in relation to insecticide resistance. Pestic Biochem Phys 2001; 70:100–7
Google Scholar | Crossref
33. Dutta, M, Rajak, P, Khatun, S, Roy, S. Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure. Chemosphere 2017; 166:255–66
Google Scholar | Crossref | Medline
34. Colhoun, EH. The physiological significance of acetylcholine in insects and observations upon other pharmacologically active substances advances in insect. Physiology 1963; 1:1–46
Google Scholar
35. Farina, M, Avila, DS, Rocha, JBT, Aschner, M. Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int 2013; 62:575–94
Google Scholar | Crossref | Medline
36. AebiH Catalase in vitro. Meth Enzymol 1984; 105:121–6
Google Scholar | Crossref | Medline
37. Yadav, SS, Kumar, R, Khare, P, Tripathi, M. Oxidative stress biomarkers in the freshwater fish, Heteropneustes fossilis (bloch) exposed to sodium fluoride: antioxidant fefense and role of ascorbic acid. Toxicol Int 2015; 22:71–6
Google Scholar | Crossref | Medline
38. Abolaji, AO, Kamdem, JP, Lugokenski, TH, Farombi, EO, Souza, DO, da Silva Loreto, EL, Rocha, J. Ovotoxicants 4-vinylcyclohexene 1,2-monoepoxide and 4-vinylcyclohexene diepoxide disrupt redox status and modify different electrophile sensitive target enzymes and genes in Drosophila melanogaster. Redox Biol 2015; 5:328–39
Google Scholar | Crossref | Medline | ISI
39. Garcia-Garcia, A, Zavala-Flores, L, Rodriguez-Rocha, H, Franco, R. Thiol-Redox signaling, dopaminergic cell death, and Parkinson’s disease. Antioxid Redox Signal 2012; 17:1764–84
Google Scholar | Crossref | Medline
40. Jones, DP, Liang, Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med 2009; 47:1329–38
Google Scholar | Crossref | Medline
41. Erel, O, Neselioglu, S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014; 47:326–32
Google Scholar | Crossref | Medline | ISI
42. Sener, S, Akbas, A, Kilinc, F, Baran, P, Erel, O, Aktas, A. Thiol/disulfide homeostasis as a marker of oxidative stress in rosacea: a controlled spectrophotometric study. Cutan Ocul Toxicol 2019; 38:55–8
Google Scholar | Crossref | Medline
43. Buchwalow, I, Schnekenburger, J, Samoilova, V, Boecker, W, Neumann, JK. Tiemann New insight into the role of nitric oxide pathways in pancreas. Acta Histochem Cytochem 2018; 51:167–72
Google Scholar | Crossref | Medline