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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph

CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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Volume 26, Issue 5


The effect of nicotine and cotinine on human gingival fibroblasts attachment to root surfaces

Zeinab Rezaei Esfahrood
  • Department of Periodontics, Dental School, International Branch, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Amirhosein Zamanian / Maryam Torshabi
  • Corresponding author
  • Department of Dental Biomaterial, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maryam Abrishami
Published Online: 2015-01-10 | DOI: https://doi.org/10.1515/jbcpp-2014-0120


Background: Different compounds of smoking (e.g., nicotine and cotinine) are risk factors for various diseases such as oral cancer and periodontal diseases. Some studies reported the negative effects of nicotine on cell proliferation and differentiation. The present in vitro study assessed the effects of nicotine and cotinine (long-acting metabolite of nicotine) on the attachment and viability of human gingival fibroblast (HGF) cells to tooth root surfaces.

Methods: A total of 70 teeth specimens were placed into 48-well culture plates and covered with HGF cell suspension, in complete Dulbecco’s modified Eagle’s medium culture medium containing 1 nM, 1 μm, 1 mM, and 5 mM of nicotine and cotinine concentrations. Cellular attachment and viability measured using an MTT assay and a scanning electron microscope were used for cell morphological evaluation.

Results: After 24 h, low (nanomolar and micromolar) and high concentrations (millimolar) of nicotine and cotinine caused a significant reduction in the initial cell adhesion in comparison with the control group, but no significant difference was observed between the nicotine and the cotinine groups (p<0.05). Dentally attached cells with low concentrations of nicotine and cotinine proliferated 48 h after exposure, the same as the control group. However, dentally attached cells with high concentrations of nicotine and cotinine (especially 5 mM) did not proliferate 24 h after exposure (p<0.05).

Conclusions: Low concentrations of nicotine and cotinine caused a reduction in the initial cell adhesion. However, no significant adverse effects on the proliferation of attached cells were seen in the longer period. High concentrations of nicotine and cotinine have adverse effects on the cell adhesion and proliferation of HGF cells.

Keywords: cotinine; fibroblast; nicotine


  • 1.

    Genco RJ. Current view of risk factors for periodontal diseases. J Periodontol 1996;67:1041–9.PubMedCrossrefGoogle Scholar

  • 2.

    Armitage AK, Dollery CT, George CF, Houseman TH, Lewis PJ, Turner DM. Absorption and metabolism of nicotine from cigarettes. Br Med J 1975;4:313–6.CrossrefPubMedGoogle Scholar

  • 3.

    Cattaneo V, Cetta G, Rota C, Vezzoni F, Rota MT, Gallanti A, et al. Volatile components of cigarette smoke: effect of acrolein and acetaldehyde on human gingival fibroblasts in vitro. J Periodontol 2000;71:425–32.CrossrefPubMedGoogle Scholar

  • 4.

    Benowitz NL. Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol 1996;36:597–613.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 5.

    Wall MA, Johnson J, Jacob P, Benowitz NL. Cotinine in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers. Am J Public Health 1988;78:699–701.PubMedCrossrefGoogle Scholar

  • 6.

    Curvall M, Enzell CR. Monitoring absorption by means of determination of nicotine and cotinine. Arch Toxicol Suppl 1986;9:88–102.PubMedCrossrefGoogle Scholar

  • 7.

    González YM, De Nardin A, Grossi SG, Machtei EE, Genco RJ, De Nardin E. Serum cotinine levels, smoking, and periodontal attachment loss. J Dent Res 1996;75:796–802.PubMedCrossrefGoogle Scholar

  • 8.

    James JA, Sayers NM, Drucker DB, Hull PS. Effects of tobacco products on the attachment and growth of periodontal ligament fibroblasts. J Periodontol 1999;70:518–25.PubMedCrossrefGoogle Scholar

  • 9.

    McGuire JR, McQuade MJ, Rossmann JA, Garnick JJ, Sutherland DE, Scheidt MJ, et al. Cotinine in saliva and gingival crevicular fluid of smokers with periodontal disease. J Periodontol 1989;60:176–81.PubMedCrossrefGoogle Scholar

  • 10.

    Rivera-Hidalgo F. Smoking and periodontal disease. Periodontol 2000 2003;32:50–8.CrossrefGoogle Scholar

  • 11.

    Grossi SG, Skrepcinski FB, DeCaro T, Zambon JJ, Cummins D, Genco RJ. Response to periodontal therapy in diabetics and smokers. J Periodontol 1996;67:1094–102.PubMedCrossrefGoogle Scholar

  • 12.

    Chang YC, Huang FM, Tai KW, Yang LC, Chou MY. Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast cultures in vitro. J Periodontal Res 2002;37:279–85.PubMedCrossrefGoogle Scholar

  • 13.

    Giannopoulou C, Geinoz A, Cimasoni G. Effects of nicotine on periodontal ligament fibroblasts in vitro. J Clin Periodontol 1999;26:49–55.PubMedCrossrefGoogle Scholar

  • 14.

    Lahmouzi J, Simain-Sato F, Defresne MP, De Pauw MC, Heinen E, Grisar T, et al. Effect of nicotine on rat gingival fibroblasts in vitro. Connect Tissue Res 2000;41:69–80.PubMedCrossrefGoogle Scholar

  • 15.

    Peacock ME, Sutherland DE, Schuster GS, Brennan WA, O’Neal RB, Strong SL, et al. The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro. J Periodontol 1993;64:658–65.PubMedCrossrefGoogle Scholar

  • 16.

    Raulin LA, McPherson JC 3rd, McQuade MJ, Hanson BS. The effect of nicotine on the attachment of human fibroblasts to glass and human root surfaces in vitro. J Periodontol 1988;59:318–25.PubMedGoogle Scholar

  • 17.

    Kim BS, Kim SJ, Kim HJ, Lee SJ, Park YJ, Lee J, et al. Effects of nicotine on proliferation and osteoblast differentiation in human alveolar bone marrow-derived mesenchymal stem cells. Life Sci 2012;90:109–15.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 18.

    Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R. Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab 2009;27:555–61.PubMedCrossrefGoogle Scholar

  • 19.

    Yanagita M, Kojima Y, Kawahara T, Kajikawa T, Oohara H, Takedachi M, et al. Suppressive effects of nicotine on the cytodifferentiation of murine periodontal ligament cells. Oral Dis 2010;16:812–7.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 20.

    Alpar B, Leyhausen G, Sapotnick A, Günay H, Geurtsen W. Nicotine- induced alterations in human primary periodontal ligament and gingiva fibroblast cultures. Clin Oral Investig 1998;2:40–6.PubMedCrossrefGoogle Scholar

  • 21.

    Tipton DA, Dabbous MK. Effects of nicotine on proliferation and extracellular matrix production of human gingival fibroblasts in vitro. J Periodontol 1995;66:1056–64.PubMedCrossrefGoogle Scholar

  • 22.

    Silva D, Cáceres M, Arancibia R, Martínez C, Martínez J, Smith PC. Effects of cigarette smoke and nicotine on cell viability, migration and myofibroblastic differentiation. J Periodontal Res 2012;47:599–607.Web of ScienceCrossrefPubMedGoogle Scholar

  • 23.

    Argentin G, Cicchetti R. Evidence for the role of nitric oxide in antiapoptotic and genotoxic effect of nicotine on human gingival fibroblasts. Apoptosis 2006;11:1887–97.PubMedCrossrefGoogle Scholar

  • 24.

    Tanur E, McQuade MJ, McPherson JC, Al-Hashimi IH, Rivera-Hidalgo F. Effects of nicotine on the strength of attachment of gingival fibroblasts to glass and non-diseased human root surfaces. J Periodontol 2000;71:717–22.CrossrefPubMedGoogle Scholar

  • 25.

    Martinez AE, Silverio KG, Fogo JC, Kirkwood KL, Rossa C Jr. Root surface conditioning with nicotine or cotinine reduces viability and density of fibroblasts in vitro. Clin Oral Investig 2005;9:180–6.PubMedCrossrefGoogle Scholar

  • 26.

    Giannopoulou C, Roehrich N, Mombelli A. Effect of nicotine-treated epithelial cells on the proliferation and collagen production of gingival fibroblasts. J Clin Periodontol 2001;28:769–75.PubMedCrossrefGoogle Scholar

  • 27.

    Theilig C, Bernd A, Ramirez-Bosca A, Görmar FF, Bereiter-Hahn J, Keller-Stanislawski B, et al. Reactions of human keratinocytes in vitro after application of nicotine. Skin Pharmacol 1994;7: 307–15.PubMedCrossrefGoogle Scholar

  • 28.

    Hanes PJ, Schuster GS, Lubas S. Binding, uptake, and release of nicotine by human gingival fibroblasts. J Periodontol 1991;62:147–52.PubMedCrossrefGoogle Scholar

  • 29.

    Chamson A, Garrone R, Auger C, Frey J. Effects of tobacco smoke extracts on the ultrastructure of fibroblasts in culture. J Submicros Cytol 1980;12:401–6.Google Scholar

  • 30.

    Ramp WK, Lenz LG, Galvin RJ. Nicotine inhibits collagen synthesis and alkaline phosphatase activity, but stimulates DNA synthesis in osteoblast-like cells. Proc Soc Exp Biol Med 1991;197:36–43.PubMedCrossrefGoogle Scholar

  • 31.

    Fang MA, Frost PJ, Iida-Klein A, Hahn TJ. Effects of nicotine on cellular function in UMR 106-01 osteoblast-like cells. Bone 1991;12:283–6.CrossrefGoogle Scholar

About the article

Corresponding author: Maryam Torshabi, Department of Dental Biomaterial, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Phone: +98-9122008324, E-mail:

Received: 2014-11-03

Accepted: 2014-11-20

Published Online: 2015-01-10

Published in Print: 2015-09-01

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 26, Issue 5, Pages 517–522, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2014-0120.

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