Reactive Oxygen Species and Antioxidant Systems in Periodontal Disease

  • Masaichi-Chang-il LeeEmail author
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


Oxidative stress induced by reactive oxygen species (ROS) is thought to play a role in the pathogenesis of various age-related diseases, including periodontitis. Many reports have suggested that dietary antioxidant deficiency results in oxidative damage at the tissue level in association with periodontal disease. Furthermore, treatment with antioxidants has been shown to prevent pathophysiological changes associated with periodontal disease and promote functional recovery in in vitro studies, animal models, and clinical trials in humans. It is therefore possible that antioxidants could be successfully used in clinical practice for the treatment or prevention of ROS-related diseases such as periodontal disease. The development of potential therapeutic antioxidants for periodontal disease requires screening using direct methods for ROS detection and appropriate animal models.


Reactive Oxygen Species Electron Spin Resonance Periodontal Disease Periodontal Tissue Gingival Crevicular Fluid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by a Grant-in-Aid for Scientific Research (no. 18592149 to M.L., no. 19592371 to T.K. & M.L., no. 23593049 to T.K., no. 23660047 to M.L.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.


  1. 1.
    Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82:291–295PubMedGoogle Scholar
  3. 3.
    Halliwell B (2009) The wanderings of a free radical. Free Radic Biol Med 46:531–542PubMedCrossRefGoogle Scholar
  4. 4.
    Nibali L, Donos N (2013) Periodontitis and redox status: a review. Curr Pharm Des 19:2687–2697PubMedCrossRefGoogle Scholar
  5. 5.
    Altman LC, Baker C, Fleckman P et al (1992) Neutrophil-mediated damage to human gingival epithelial cells. J Periodontal Res 27:70–79PubMedCrossRefGoogle Scholar
  6. 6.
    Liu RK, Cao CF, Meng HX et al (2001) Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis. J Periodontol 72:1545–1553PubMedCrossRefGoogle Scholar
  7. 7.
    Battino M, Bullon P, Wilson M et al (1999) Oxidative injury and inflammatory periodontal diseases: the challenge of anti-oxidants to free radicals and reactive oxygen species. Crit Rev Oral Biol Med 10:458–476PubMedCrossRefGoogle Scholar
  8. 8.
    Lee MC (2013) Assessment of oxidative stress and antioxidant property using electron spin resonance (ESR) spectroscopy. J Clin Biochem Nutr 52:1–8PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Sugiyama S, Takahashi SS, Tokutomi FA et al (2012) Gingival vascular functions are altered in type 2 diabetes mellitus model and/or periodontitis model. J Clin Biochem Nutr 51:108–113PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Yoshino F, Yoshida A, Wada-Takahashi S et al (2012) Assessments of salivary antioxidant activity using electron spin resonance spectroscopy. Arch Oral Biol 57:654–662PubMedCrossRefGoogle Scholar
  11. 11.
    Fridovich I (1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64:97–112PubMedCrossRefGoogle Scholar
  12. 12.
    Huie RE, Padmaja S (1993) The reaction of no with superoxide. Free Radic Res 18:195–199CrossRefGoogle Scholar
  13. 13.
    Massey V (1994) Activation of molecular oxygen by flavins and flavoproteins. J Biol Chem 269:22459–22462PubMedGoogle Scholar
  14. 14.
    Halliwell B, Gutteridge JMC (eds) (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, OxfordGoogle Scholar
  15. 15.
    Dikalov S, Griendling KK, Harrison DG (2007) Measurement of reactive oxygen species in cardiovascular studies. Hypertension 49:717–727PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Serrander L, Jaquet V, Bedard K et al (2007) NOX5 is expressed at the plasma membrane and generates superoxide in response to protein kinase C activation. Biochimie 89:1159–1167PubMedCrossRefGoogle Scholar
  17. 17.
    Frey RS, Ushio-Fukai M, Malik AB (2009) NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology. Antioxid Redox Signal 11:791–810PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Gongora MC, Qin Z, Laude K et al (2006) Role of extracellular superoxide dismutase in hypertension. Hypertension 48:473–481PubMedCrossRefGoogle Scholar
  19. 19.
    Hawkins BJ, Madesh M, Kirkpatrick CJ et al (2007) Superoxide flux in endothelial cells via the chloride channel-3 mediates intracellular signaling. Mol Biol Cell 18:2002–2012PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Giannopoulou C, Krause KH, Muller F (2008) The NADPH oxidase NOX2 plays a role in periodontal pathologies. Semin Immunopathol 30:273–278PubMedCrossRefGoogle Scholar
  21. 21.
    Cai X, Li C, Du G et al (2008) Protective effects of baicalin on ligature-induced periodontitis in rats. J Periodontal Res 43:14–21PubMedGoogle Scholar
  22. 22.
    Miller FJ Jr, Filali M, Huss GJ et al (2007) Cytokine activation of nuclear factor kappa B in vascular smooth muscle cells requires signaling endosomes containing Nox1 and ClC-3. Circ Res 101:663–671PubMedCrossRefGoogle Scholar
  23. 23.
    Hilenski LL, Clempus RE, Quinn MT et al (2004) Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 24:677–683PubMedCrossRefGoogle Scholar
  24. 24.
    Chamulitrat W, Schmidt R, Tomakidi P et al (2003) Association of gp91phox homolog Nox1 with anchorage-independent growth and MAP kinase-activation of transformed human keratinocytes. Oncogene 22:6045–6053PubMedCrossRefGoogle Scholar
  25. 25.
    Nakano Y, Banfi B, Jesaitis AJ et al (2007) Critical roles for p22phox in the structural maturation and subcellular targeting of Nox3. Biochem J 403:97–108PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Kuo LY, Hwang GY, Yang SL et al (2004) Inactivation of Bacillus stearothermophilus leucine aminopeptidase II by hydrogen peroxide and site-directed mutagenesis of methionine residues on the enzyme. Protein J 23:295–302PubMedCrossRefGoogle Scholar
  27. 27.
    Stadtman ER, Berlett BS (1997) Reactive oxygen-mediated protein oxidation in aging and disease. Chem Res Toxicol 10:485–494PubMedCrossRefGoogle Scholar
  28. 28.
    Kang LS, Reyes RA, Muller-Delp JM (2009) Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2. Am J Physiol Heart Circ Physiol 297:H1087–H1095PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Thengchaisri N, Kuo L (2003) Hydrogen peroxide induces endothelium-dependent and -independent coronary arteriolar dilation: role of cyclooxygenase and potassium channels. Am J Physiol Heart Circ Physiol 285:H2255–H2263PubMedGoogle Scholar
  30. 30.
    Csordas G, Hajnoczky G (2009) SR/ER-mitochondrial local communication: calcium and ROS. Biochim Biophys Acta 1787:1352–1362PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Muller G, Morawietz H (2009) NAD(P)H oxidase and endothelial dysfunction. Horm Metab Res 41:152–158PubMedCrossRefGoogle Scholar
  32. 32.
    Storz P (2006) Reactive oxygen species-mediated mitochondria-to-nucleus signaling: a key to aging and radical-caused diseases. Sci STKE 2006:re3PubMedGoogle Scholar
  33. 33.
    Hecquet CM, Ahmmed GU, Vogel SM et al (2008) Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circ Res 102:347–355PubMedCrossRefGoogle Scholar
  34. 34.
    Wolin MS, Gupte SA, Oeckler RA (2002) Superoxide in the vascular system. J Vasc Res 39:191–207PubMedCrossRefGoogle Scholar
  35. 35.
    Lu F (2007) Reactive oxygen species in cancer, too much or too little? Med Hypotheses 69:1293–1298PubMedCrossRefGoogle Scholar
  36. 36.
    Vincent A, Crozatier M (2010) Neither too much nor too little: reactive oxygen species levels regulate Drosophila hematopoiesis. J Mol Cell Biol 2:74–75PubMedCrossRefGoogle Scholar
  37. 37.
    Johansen JS, Harris AK, Rychly DJ et al (2005) Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 4:5PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Rhee SG, Bae YS, Lee SR et al (2000) Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE 2000:pe1PubMedGoogle Scholar
  39. 39.
    Ventura A, Pelicci PG (2002) Semaphorins: green light for redox signaling? Sci STKE 2002:pe44PubMedGoogle Scholar
  40. 40.
    Niki E (2010) Assessment of antioxidant capacity in vitro and in vivo. Free Radic Biol Med 49:503–515PubMedCrossRefGoogle Scholar
  41. 41.
    Seymour GJ, Whyte GJ, Powell RN (1986) Chemiluminescence in the assessment of polymorphonuclear leukocyte function in chronic inflammatory periodontal disease. J Oral Pathol 15:125–131PubMedCrossRefGoogle Scholar
  42. 42.
    Tsai CC, Chen HS, Chen SL et al (2005) Lipid peroxidation: a possible role in the induction and progression of chronic periodontitis. J Periodontal Res 40:378–384PubMedCrossRefGoogle Scholar
  43. 43.
    Sawamoto Y, Sugano N, Tanaka H et al (2005) Detection of periodontopathic bacteria and an oxidative stress marker in saliva from periodontitis patients. Oral Microbiol Immunol 20:216–220PubMedCrossRefGoogle Scholar
  44. 44.
    Wolfram RM, Budinsky AC, Eder A et al (2006) Salivary isoprostanes indicate increased oxidation injury in periodontitis with additional tobacco abuse. Biofactors 28:21–31PubMedCrossRefGoogle Scholar
  45. 45.
    Tomofuji T, Ekuni D, Sanbe T et al (2009) Effects of vitamin C intake on gingival oxidative stress in rat periodontitis. Free Radic Biol Med 46:163–168PubMedCrossRefGoogle Scholar
  46. 46.
    Ekuni D, Tomofuji T, Sanbe T et al (2009) Periodontitis-induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosis. J Periodontal Res 44:434–442PubMedCrossRefGoogle Scholar
  47. 47.
    Galli C, Passeri G, Macaluso GM (2011) FoxOs, Wnts and oxidative stress-induced bone loss: new players in the periodontitis arena? J Periodontal Res 46:397–406PubMedCrossRefGoogle Scholar
  48. 48.
    Akalin FA, Toklu E, Renda N (2005) Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls. J Clin Periodontol 32:238–243PubMedCrossRefGoogle Scholar
  49. 49.
    Tonguc MO, Ozturk O, Sutcu R et al (2011) The impact of smoking status on antioxidant enzyme activity and malondialdehyde levels in chronic periodontitis. J Periodontol 82:1320–1328PubMedCrossRefGoogle Scholar
  50. 50.
    Amarasena N, Ogawa H, Yoshihara A et al (2005) Serum vitamin C-periodontal relationship in community-dwelling elderly Japanese. J Clin Periodontol 32:93–97PubMedCrossRefGoogle Scholar
  51. 51.
    Ekuni D, Tomofuji T, Sanbe T et al (2009) Vitamin C intake attenuates the degree of experimental atherosclerosis induced by periodontitis in the rat by decreasing oxidative stress. Arch Oral Biol 54:495–502PubMedCrossRefGoogle Scholar
  52. 52.
    Singh N, Narula SC, Sharma RK et al (2013) Vitamin E supplementation, superoxide dismutase status and outcome of scaling and root planing in chronic periodontitis patients: a randomized clinical trial. J Periodontol DOI:10.1902/job2013.120727:1-10Google Scholar
  53. 53.
    de Carvalho Rde S, de Souza CM, Neves JC et al (2013) Vitamin E does not prevent bone loss and induced anxiety in rats with ligature-induced periodontitis. Arch Oral Biol 58:50–58PubMedCrossRefGoogle Scholar
  54. 54.
    Hirasawa M, Takada K, Makimura M et al (2002) Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study. J Periodontal Res 37:433–438PubMedCrossRefGoogle Scholar
  55. 55.
    Di Paola R, Mazzon E, Zito D et al (2005) Effects of Tempol, a membrane-permeable radical scavenger, in a rodent model periodontitis. J Clin Periodontol 32:1062–1068PubMedCrossRefGoogle Scholar
  56. 56.
    Kim do Y, Jun JH, Lee HL et al (2007) N-acetylcysteine prevents LPS-induced pro-inflammatory cytokines and MMP2 production in gingival fibroblasts. Arch Pharm Res 30:1283–1292PubMedCrossRefGoogle Scholar
  57. 57.
    Cheng WC, Huang RY, Chiang CY et al (2010) Ameliorative effect of quercetin on the destruction caused by experimental periodontitis in rats. J Periodontal Res 45:788–795PubMedCrossRefGoogle Scholar
  58. 58.
    Govindaraj J, Emmadi P, Deepalakshmi et al (2010) Protective effect of proanthocyanidins on endotoxin induced experimental periodontitis in rats. Indian J Exp Biol 48:133–142PubMedGoogle Scholar
  59. 59.
    Kasuyama K, Tomofuji T, Ekuni D et al (2011) Hydrogen-rich water attenuates experimental periodontitis in a rat model. J Clin Periodontol 38:1085–1090PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Yokosuka-Shonan Disaster Health Emergency Research Center & ESR LaboratoriesKanagawa Dental UniversityYokosukaJapan

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