Advertisement

Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis

  • Cenk Fatih ÇanakçiEmail author
  • Varol Çanakçi
  • Abdulgani Tatar
  • Abubekir Eltas
  • Ufuk Sezer
  • Yasin Çiçek
  • Sitki Oztas
Open Access
Original Article

Abstract

Introduction:

Oxidative stress may contribute to the pathogenesis of periodontitis. However, the detailed molecular mechanism remains unclear. Both 8-hydroxydeoxyguanosine (8-OHdG) and mitochondrial DNA (mtDNA) deletion have been reported as early oxidative DNA damage markers. In this study, 8-OHdG levels in saliva and mtDNA deletions in gingival tissue of patients with chronic periodontitis (CP) were evaluated.

Materials and Methods:

Gingival tissue and whole saliva samples were collected from 32 patients with CP and 32 healthy control subjects. To determine the clinical condition of each subject, the plaque index, gingival index, clinical attachment level (CAL), and probing depth (PD) were measured. Using the ELISA and polymerase chain reaction methods, the salivary 8-OHdG levels and the 7.4-kbp and 5-kbp mtDNA deletions were examined.

Results:

The 5-kbp mtDNA deletion was detected in 20 of the 32 periodontitis patients (62.5%), but was not detected in the healthy controls. The mean value of 8-OHdG in the saliva of the periodontitis patients with deleted mtDNA was significantly higher than in the patients with non-deleted mtDNA (p<0.01). Also, significant correlation was found between the occurrence of the 5-kbp mtDNA deletion and salivary 8-OHdG levels (p<0.01). Similar correlations were detected between salivary 8-OHdG levels and age, PD, and CAL (p<0.01, p<0.05).

Conclusion:

Increased oxidative stress may lead to premature oxidative DNA damage in the gingival tissue of periodontitis patients and the salivary 8-OHdG level may signify premature oxidative mtDNA damage in diseased gingival tissue.

Keywords

periodontitis gingiva saliva 8-hydroxyguanosine mitochondrial DNA deletion oxidative DNA damage 

References

  1. Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4: 1–6PubMedCrossRefGoogle Scholar
  2. Canakci CF, Cicek Y, Canakci V (2005) Reactive oxygen species and human inflammatory periodontal diseases. Biochemistry 70: 619–628PubMedGoogle Scholar
  3. Canakci CF, Tatar A, Canakci V et al (2006) New evidence of premature oxidative DNA damage: mitochondrial DNA deletion in gingival tissue of patients with periodontitis. J Periodontol 77: 1894–1900PubMedCrossRefGoogle Scholar
  4. Chapple IL, Matthews JB (2007) The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000(43): 160–232CrossRefGoogle Scholar
  5. Chiou CC, Chang PY, Chan EC et al (2003) Urinary 8-hydroxydeoxyguanosine and its analogs as DNA marker of oxidative stress: development of an ELISA and measurement in both bladder and prostate cancers. Clin Chim Acta 334: 87–94PubMedCrossRefGoogle Scholar
  6. Dincer Y, Erzin Y, Himmetoglu S et al (2007) Oxidative DNA damage and antioxidant activity in patients with inflammatory bowel disease. Dig Dis Sci 52: 1636–1641PubMedCrossRefGoogle Scholar
  7. Jessie BC, Sun CQ, Irons HR et al (2001) Accumulation of mitochondrial DNA deletions in the malignant prostate of patients of different ages. Exp Gerontol 37: 169–174PubMedCrossRefGoogle Scholar
  8. Kakimoto M, Inoguchi T, Sonta T et al (2002) Accumulation of 8-hydroxy-2’-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats. Diabetes 2002(51): 1588–1595CrossRefGoogle Scholar
  9. Katsumata K, Hayakawa M, Tanaka M et al (1994) Fragmentation of human heart mitochondrial DNA associated with premature aging. Biochem Biophys Res Commun 202: 102–110PubMedCrossRefGoogle Scholar
  10. Lee HC, Pang CY, Hsu HS et al (1994) Differential accumulations of 4977 bp deletion in mitochondrial DNA of various tissues in human ageing. Biochim Biophys Acta 1226: 37–43PubMedGoogle Scholar
  11. Lee HC, Lim ML, Lu CY et al (1999) Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging-smoking enhances oxidative stress on the aged tissues. Arch Biochem Biophys 362: 309–316PubMedCrossRefGoogle Scholar
  12. Lim PS, Cheng YM, Wei YH (2000) Large-scale mitochondrial DNA deletions in skeletal muscle of patients with end-stage renal disease. Free Radic Biol Med 29: 454–463PubMedCrossRefGoogle Scholar
  13. Liu H, Uno M, Kitazato KT et al (2004) Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction. Brain Res 1025: 43–50PubMedCrossRefGoogle Scholar
  14. Liu TY, Chen CL, Chi CW (1996) Oxidative damage to DNA induced by areca nut extract. Mutat Res 367: 25–31PubMedCrossRefGoogle Scholar
  15. Liu VW, Zhang C, Nagley P (1998) Mutations in mitochondrial DNA accumulate differentially in three different human tissues during ageing. Nucleic Acids Res 26: 1268–1275PubMedCrossRefGoogle Scholar
  16. Löe H, Silness J (1963) Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand 21: 531–551CrossRefGoogle Scholar
  17. Miller DR, Lamster IB, Chasens AI (1984) Role of the polymorphonuclear leukocyte in periodontal health and disease. J Clin Periodontol 11: 1–15PubMedCrossRefGoogle Scholar
  18. Moseley R, Waddington RJ, Embery G (1997) Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes. Biochim Biophys Acta 1362: 221–231PubMedGoogle Scholar
  19. Nomoto K, Tsuneyama K, Takahashi H et al (2008) Cytoplasmic fine granular expression of 8-hydroxydeoxyguanosine reflects early mitochondrial oxidative DNA damage in nonalcoholic fatty liver disease. Appl Immunohistochem Mol Morphol 16: 71–75PubMedGoogle Scholar
  20. Ozmeric N (2005) Advances in periodontal disease markers. Clin Chim Acta 343: 1–16CrossRefGoogle Scholar
  21. 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
  22. Sculley DV, Langley-Evans SC (2002) Salivary antioxidants and periodontal disease status. Proc Nutr Soc 61: 137–143PubMedCrossRefGoogle Scholar
  23. Sies H (1991) Oxidative stress; oxidants and antioxidants. Academic Press, New YorkGoogle Scholar
  24. Silness J, Löe H (1964) Periodontal disease in pregnancy II. Correlation of between oral hygiene and periodontal condition. Acta Odontol Scand 22: 121–135Google Scholar
  25. Suzuki S, Hinokio Y, Kamatu K et al (1999) Oxidative damage to mitochondrial DNA and its relationship to diabetic complications. Diabetes Res Clin Pract 45: 161–168PubMedCrossRefGoogle Scholar
  26. Takane M, Sugano N, Ezawa T et al (2005) A marker of oxidative stress in saliva: association with periodontally-involved teeth of a hopeless prognosis. J Oral Sci 47: 53–57PubMedCrossRefGoogle Scholar
  27. Takane M, Sugano N, Iwasaki H et al (2002) New biomarker evidence of oxidative DNA damage in whole saliva from clinically healthy and periodontally diseased individuals. J Periodontol 73: 551–554PubMedCrossRefGoogle Scholar
  28. Wada T, Tanji N, Ozawa A et al (2006) Mitochondrial DNA mutations and 8-hydroxy-2’-deoxyguanosine Content in Japanese patients with urinary bladder and renal cancers. Anticancer Res 26: 3403–3408PubMedGoogle Scholar
  29. Wallace DC, Shoffner JM, Trounce I et al (1995) Mitochondrial DNA mutations in human degenerative diseases and aging. Biochim Biophys Acta 1271: 141–151PubMedGoogle Scholar
  30. Wang AL, Lukas TJ, Yuan M et al (2008) Increased mitochondrial DNA damage and down-regulation of DNA repair enzymes in aged rodent retinal pigment epithelium and choroid. Mol Vis 14: 644–651PubMedGoogle Scholar
  31. Wu LL, Chiou CC, Chang PY et al (2004) Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta 339: 1–9PubMedCrossRefGoogle Scholar
  32. Yakes FM, van Houten B (1997) Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94: 514–519PubMedCrossRefGoogle Scholar
  33. Yen TC, Su JH, King KL et al (1991) Ageing-associated 5 kbp deletion in human liver mitochondrial DNA. Biochem Biophys Res Commun 178: 124–131PubMedCrossRefGoogle Scholar

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2009

Authors and Affiliations

  • Cenk Fatih Çanakçi
    • 1
    • 4
    Email author
  • Varol Çanakçi
    • 1
  • Abdulgani Tatar
    • 2
  • Abubekir Eltas
    • 1
  • Ufuk Sezer
    • 3
  • Yasin Çiçek
    • 1
  • Sitki Oztas
    • 2
  1. 1.Department of Periodontology, Faculty of DentistryAtaturk UniversityErzurumTurkey
  2. 2.Department of Genetics, Faculty of MedicineAtaturk UniversityErzurumTurkey
  3. 3.Department of Periodontology, Faculty of DentistryKaradeniz Technical UniversityTrabzonTurkey
  4. 4.Diş Hekimligi Fakültesi, Periodontoloji Anabilim DaliAtatürk ÜniversitesiErzurumTurkey

Personalised recommendations