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Boric Acid Reverses Nicotine-Induced Cytokine Expressions of Human Gingival Fibroblasts

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Abstract

Nicotine, the major bioactive ingredient in tobacco, is a major risk factor for periodontal disease and destruction. Nicotine has been shown to stimulate the production of cytokines that are priming agents for inflammation that induces tissue destruction, such as IL-1β, IL-6, and IL-8, by gingival keratinocytes and human gingival fibroblasts (HGF). Boron as boric acid has been found to decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in cells with inflammatory stress. Thus, a study was performed to determine whether boric acid reverses negative effects of nicotine on human gingival fibroblasts (HGFs). The viability and cytokine expressions of HGFs cultured for 24 and 72 h in control medium with no nicotine or boric acid added and in media containing only nicotine, only boric acid, or a combination of BA and nicotine were determined. Nicotine in concentrations of 10−1, 10−2, 10−3,10−4, 10−5, and 10–6 mM significantly reduced cell viability compared to the control. Boric acid at 10 and 50 ng/mL in the media partially restored and 100 ng/mL in the media fully restored the nicotine-depressed HGF cell viability to the same level as the control group. Nicotine elevated the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8, and IL-17 and decreased the anti-inflammatory IL-10 in HGFs at 24 and 72 h. Boric acid at 100 ng/mL in the medium prevented the changes induced by nicotine alone. The findings indicate that boric acid can inhibit or reverse nicotine-induced pathology in periodontal tissue and thus may help maintain oral and periodontal health in tobacco users.

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References

  1. Gurusamy R, Natarajan S (2013) Current status on biochemistry and molecular biology of microbial degradation of nicotine. Sci World J 2013:125385

    Article  Google Scholar 

  2. Sutton JD, Salas Martinez ML, Gerkovich MM (2017) Environmental tobacco smoke and periodontitis in United States non-smokers, 2009 to 2012. J Periodontol 88:565–574

    Article  Google Scholar 

  3. Akinkugbe AA, Sanders AE, Preisser JS, Cai J, Salazar CR, Beck JD (2017) Environmental tobacco smoke exposure and periodontitis prevalence among nonsmokers in the hispanic community Health Study/Study of Latinos. Community Dent Oral Epidemiol 45:168–177

    Article  Google Scholar 

  4. Akinkugbe AA, Slade GD, Divaris K, Poole C (2016) Systematic review and meta-analysis of the association between exposure to environmental tobacco smoke and periodontitis endpoints among nonsmokers. Nicotine Tob Res 18:2047–2056

    Article  Google Scholar 

  5. Zhang Y, He J, He B, Huang R, Li M (2019) Effect of tobacco on periodontal disease and oral cancer. Tob Induc Dis 17:40

    Article  Google Scholar 

  6. Bozkurt SB, Hakki SS (2020) Nicotine suppresses proliferation and mineralized tissue-associated gene expressions of cementoblasts. J Periodontol 91:800–808

    Article  CAS  Google Scholar 

  7. Johnson GK, Guthmiller JM, Joly S, Organ CC, Dawson DV (2010) Interleukin-1 and interleukin-8 in nicotine- and lipopolysaccharide-exposed gingival keratinocyte cultures. J Periodontal Res 45:583–588

    CAS  Google Scholar 

  8. Pan W, Wang Q, Chen Q (2019) The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci 11(3):30

    Article  CAS  Google Scholar 

  9. Almasri A, Wisithphrom K, Windsor LJ, Olson B (2007) Nicotine and lipopolysaccharide affect cytokine expression from gingival fibroblasts. J Periodontol 78:533–541

    Article  CAS  Google Scholar 

  10. Giannopoulou C, Cappuyns I, Mombelli A (2003) Effect of smoking on gingival crevicular fluid cytokine profile during experimental gingivitis. J Clin Periodontol 30(11):996–1002

    Article  CAS  Google Scholar 

  11. Bergström J (2004) Tobacco smoking and chronic destructive periodontal disease. Odontology 92:1–8

    Article  Google Scholar 

  12. Dinca L, Scorei R (2013) Boron in human nutrition and its regulations use. J Nutr Ther 2:22–29

    CAS  Google Scholar 

  13. Hacioglu C, Kar F, Kacar S, Sahinturk V, Kanbak G (2020) High concentrations of boric acid trigger concentration-dependent oxidative stress, apoptotic pathways and morphological alterations in DU-145 Human Prostate Cancer Cell Line. Biol Trace Elem Res 193(2):400–409

    Article  CAS  Google Scholar 

  14. Hakki SS, Nielsen FH (2020) Anti-inflammatory and anti-microbial potentials of boron in medicine and dentistry. Boron and Human Health. Chapter 5, pages; 67–82, Editor: Mehmet Korkmaz. Nobel publishing

  15. Benderdour M, Hess K, Dzondo-Gadet M, Nabet P, Belleville F, Dousset B (1998) Boron modulates extracellular matrix and TNF alpha synthesis in human fibroblasts. Biochem Biophys Res Commun 246(3):746–751

    Article  CAS  Google Scholar 

  16. Bourgeois A-C, Scott M-E, Sabally K, Koski K-G (2007) Low dietary boron reduces parasite (nematoda) survival and alters cytokine profiles but the infection modifies liver minerals in mice. J Nutr 137(9):2080–2086

    Article  CAS  Google Scholar 

  17. Cao J, Jiang L, Zhang X, Yao X, Geng C, Xue X, Zhong L (2008) Boric acid inhibits LPS-induced TNF-alpha formation through a thiol-dependent mechanism in THP-1 cells. J Trace Elem Med Biol 22(3):189–195

    Article  CAS  Google Scholar 

  18. Scorei RI, Ciofrangeanu C, Ion R, Cimpean A, Galateanu B, Mitran V, Iordachescu D (2010) In vitro effects of calcium fructoborate upon production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages. Biol Trace Elem Res 135(1–3):334–344

    Article  CAS  Google Scholar 

  19. Rogoveanu O-C, Mofoşanu GD, Bejenaru C, Bejenaru LE, Croitoru O, Neamţu J, Pietrzkowski Z, Reyes-Izquierdo T, Biţa A, Scorei ID, Scorei R (2015) Effects of calcium fructoborate on levels of C-reactive protein, total cholesterol, low-density lipoprotein, triglycerides, IL-1B, IL-6, and MCP-1: a double-blind, placebo-controlled clinical study. Biol Trace Elem Res 163:124–131

    Article  CAS  Google Scholar 

  20. Bozkurt SB, Hakki SS, Hakki EE, Durak Y, Kantarci A (2017) Porphyromonas gingivalis lipopolysaccharide induces a pro-inflammatory human gingival fibroblast phenotype. Inflammation 40:144–153

    Article  CAS  Google Scholar 

  21. Torshabi M, Esfahrood ZR, Jamshidi M, Torshizi AM, Sotoudeh S (2017) Efficacy of vitamins E and C for reversing the cytotoxic effects of nicotine and cotinine. Eur J Oral Sci 125(6):426–437

    Article  CAS  Google Scholar 

  22. Kim B-S, Kim S-J, Kim H-J, Lee S-J, Park Y-J, Lee J, You H-K (2012) Effects of nicotine on proliferation and osteoblast differentiation in human alveolar bone marrow-derived mesenchymal stem cells. Life Sci 90(3–4):109–115

    Article  CAS  Google Scholar 

  23. Tomar SL, Asma S (2000) Smoking-attributable periodontitis in the United States: findings from NHANES III. National health and nutrition examination survey. J Periodontol 71:743–751

    Article  CAS  Google Scholar 

  24. Leite FRM, Nascimento GG, Scheutz F, López R (2018) Effect of smoking on periodontitis: a systematic review and meta-regression. Am J Prev Med 54(6):831–841

    Article  Google Scholar 

  25. Holliday RS, Campbell J, Preshaw PM (2019) Effect of nicotine on human gingival, periodontal ligament and oral epithelial cells. A systematic review of the literature. J Dent 86:81–88

    Article  CAS  Google Scholar 

  26. Lee H-J, Guo H-Y, Lee S-K, Jeon B-H, Jun C-D, Lee S-K, Park M-H, Kim E-C (2002) Effects of nicotine on proliferation, cell cycle, and differentiation in immortalized and malignant oral keratinocytes. J Oral Pathol Med 34:436–443

    Article  Google Scholar 

  27. Kang SW, Park HJ, Ban JY, Chung JH, Chun GS, Cho JO (2011) Effects of nicotine on apoptosis in human gingival fibroblasts. Arch Oral Biol 56:1091–1097

    Article  CAS  Google Scholar 

  28. Figueredo CM, Lira-Junior R, Love RM (2019) T and B Cells in periodontal disease: new functions in a complex scenario. Int J Mol Sci 20(16):3949

    Article  CAS  Google Scholar 

  29. Finoti LS, Nepomuceno R, Pigossi SC, Corbi SC, Secolin R, Scarel-Caminaga RM (2017) Association between interleukin-8 levels and chronic periodontal disease: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 96(22):e6932

    Article  CAS  Google Scholar 

  30. Wendell KJ, Stein SH (2001) Regulation of cytokine production in human gingival fibroblasts following treatment with nicotine and lipopolysaccharide. J Periodontol 72:1038–1044

    Article  CAS  Google Scholar 

  31. Cardoso EM, Reis C, Manzanares-Céspedes MC (2018) Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. Postgrad Med 130(1):98–104

    Article  Google Scholar 

  32. Torshabi M, Esfahrood ZR, Jamshidi M, Torshizi AM, Sotoudeh S (2017) Efficacy of vitamins E and C for reversing the cytotoxic effects of nicotine and cotinine. Eur J Oral Sci 125:426–437

    Article  CAS  Google Scholar 

  33. Park G-J, Kim Y-S, Kang K-L, Bae S-J, Baek H-S, Auh Q-S, Chun Y-H, Park B-H, Kim E-C (2013) Effects of sirtuin 1 activation on nicotine and lipopolysaccharide-induced cytotoxicity and inflammatory cytokine production in human gingival fibroblasts. J Periodontal Res 48:483–492

    Article  CAS  Google Scholar 

  34. Hakki SS, Bozkurt SB, Hakki EE (2010) Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1). J Trace Elem Med Biol 24:243–250

    Article  CAS  Google Scholar 

  35. Sağlam M, Arslan U, Bozkurt SB, Hakki SS (2012) Boric acid irrigation as an adjunct to mechanical periodontal therapy in patients with chronic periodontitis: a randomized clinical trial. J Periodontol 84:1297–1308

    Article  Google Scholar 

  36. Nielsen FH (2020) Manganese, molybdenum, boron, silicon, and other trace elements. In: Marriott BP, Birt DF, Stallings VA, Yates AA (eds) Present Knowledge in Nutrition, vol 1, 11th edn. Elsevier, Amsterdam, pp 485–502

    Chapter  Google Scholar 

  37. Kent LW, Rahemtulla F, Michalek SM (1999) Interleukin (IL)-1 and porphyromonas gingivalis lipopolysaccharide stimulation of IL-6 production by fibroblasts derived from healthy or periodontally diseased human gingival tissue. J Periodontol 70:274–282

    Article  CAS  Google Scholar 

  38. Dongari-Bagtzoglou AI, Ebersole JL (1998) Increased presence of interleukin-6 (IL-6) and IL-8 secreting fibroblast subpopulations in adult periodontitis. J Periodontol 69:899–910

    Article  CAS  Google Scholar 

  39. Fletcher J, Reddi K, Poole S, Nair S, Henderson B, Tabona P, Wilson M (1997) Interactions between periodontopathogenic bacteria and cytokines. J Periodontal Res 32(1 Pt 2):200–205

    Article  CAS  Google Scholar 

  40. Zee K-Y (2009) Smoking and periodontal disease. Aust Dent J 54:44–50

    Article  Google Scholar 

Download references

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Correspondence to Serife Buket Bozkurt.

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The study was approved by the Ethics Committee of the Faculty of Dentistry (2008/145) of Selcuk University. Informed consent was obtained individuals providing explant cultures of gingiva.

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The authors declare no competing interests.

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Bozkurt, S.B., Nielsen, F.H. & Hakki, S.S. Boric Acid Reverses Nicotine-Induced Cytokine Expressions of Human Gingival Fibroblasts. Biol Trace Elem Res 201, 1174–1180 (2023). https://doi.org/10.1007/s12011-022-03243-1

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