J Menopausal Med.  2017 Apr;23(1):32-41. 10.6118/jmm.2017.23.1.32.

Comparative Evaluation of Salivary Neopterin Levels and Its Effects to Periodontal Therapy in Pre- and Post-Menopausal Women

• Prasanna J
• Sumadhura
• Karunakar
• Rohini N

• KMID: 2378222
• DOI: http://doi.org/10.6118/jmm.2017.23.1.32

Abstract

OBJECTIVES
Neopterin is a valuable diagnostic biomarker, which is elevated in inflammatory conditions like periodontitis, that is characterized by destruction of the supporting structures of the teeth. Among the biomarkers, neopterin occurs in body fluids, and acts as a diagnostic marker for present and future disease activity.
METHODS
Thirty female subjects with chronic periodontitis, mean age 50 years (40-60 years) were included in this study. Depending upon their menstrual history, subjects were categorized into two groups of fifteen each. Group I 15 pre-menopausal women, and Group II 15 post-menopausal women. Saliva was collected, and neopterin levels were assessed by enzyme-linked immunosorbent assay in both the groups, at base line and after three months of nonsurgical periodontal therapy (NSPT). Periodontal parameters like pocket probing depth (PD) and Russell's periodontal disease index (PDI) were assessed before treatment as well as after three months of scaling and root planning.
RESULTS
Intra group analysis showed significant markdown in the mean values of all the parameters from baseline to three months (P < 0.001), for all patients. The intergroup comparison, from baseline to 3 months also showed no significant change in PD and PDI values, but there was a statistically significant difference in the salivary neopterin levels (P = 0.04).
CONCLUSIONS
Neopterin levels were found to be reduced in three months after NSPT in both the groups, suggesting that the NSPT is the gold standard therapy, and also that neopterin levels in saliva can be used as an indicator to identify periodontal inflammation and destruction.

Keyword

Neopterin; Periodontitis; Reactive oxygen species; Root planing; Saliva; Women's health

MeSH Terms

Biomarkers
Body Fluids
Chronic Periodontitis
Enzyme-Linked Immunosorbent Assay
Female
Humans
Inflammation
Neopterin*
Periodontal Diseases
Periodontitis
Reactive Oxygen Species
Root Planing
Saliva
Tooth
Women's Health
Biomarkers
Neopterin
Reactive Oxygen Species

Figure

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  Fig. 1 (A) Intra group comparison of salivary neopterin. (B) Intra group comparison of periodontal index.

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  Fig. 2 (A) Intra group comparison of salivary neopterin. (B) Intra group comparison of periodontal index.

• 

  Fig. 3 Salivary neopterin levels in pre- and post-menopause.

Reference

1. de Queiroz AC, Taba M Jr, O'Connell PA, da Nobrega PB, Costa PP, Kawata VK, et al. Inflammation markers in healthy and periodontitis patients: a preliminary data screening. Braz Dent J. 2008; 19:3–8.

2. Ebersole JL, Machen RL, Steffen MJ, Willmann DE. Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis. Clin Exp Immunol. 1997; 107:347–352.

3. Zhang L, Henson BS, Camargo PM, Wong DT. The clinical value of salivary biomarkers for periodontal disease. Periodontol 2000. 2009; 51:25–37.

4. Chapple IL. Periodontal diagnosis and treatment--where does the future lie? Periodontol 2000. 2009; 51:9–24.

5. Marsálek P, Svoboda M, Smutná M, Blahová J, Vecerek V. Neopterin and biopterin as biomarkers of immune system activation associated with castration in piglets. J Anim Sci. 2011; 89:1758–1762.

6. Andert SE, Müller MM. Neopterin: biochemistry and clinical usefulness. J Int Fed Clin Chem. 1995; 7:70–76.

7. Murr C, Widner B, Wirleitner B, Fuchs D. Neopterin as a marker for immune system activation. Curr Drug Metab. 2002; 3:175–187.

8. Armitage GC. Development of a classification system for periodontal diseases and conditions. Northwest Dent. 2000; 79:31–35.

9. Wei SH, Lang KP. Periodontal epidemiological indices for children and adolescents: I. Gingival and periodontal health assessments. Pediatr Dent. 1981; 3:353–360.

10. Elgün S, Ozmeriç N, Demirtaş S. Alanine aminopeptidase and dipeptidylpeptidase IV in saliva: the possible role in periodontal disease. Clin Chim Acta. 2000; 298:187–191.

11. Eisenhut M. Neopterin in diagnosis and monitoring of infectious diseases. J Biomark. 2013; 2013:196432.

12. Bodur A, Baydar T, Ozmeric N, Engin AB, Uraz A, Eren K, et al. Neopterin profile to evaluate the effectiveness of treatment in aggressive periodontitis. Pteridines. 2003; 14:77–81.

13. Sakurai A, Goto M. Neopterin: isolation from human urine. J Biochem. 1967; 61:142–145.

14. Fuchs D, Weiss G, Wachter H. Neopterin, biochemistry and clinical use as a marker for cellular immune reactions. Int Arch Allergy Immunol. 1993; 101:1–6.

15. Huber C, Batchelor JR, Fuchs D, Hausen A, Lang A, Niederwieser D, et al. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med. 1984; 160:310–316.

16. Ayling J, Nair MG, Baugh CM, editors. Chemistry and biology of pteridines and folates. New York, NY: Springer Science+Business Media New York;1993.

17. George AK, Janam P. The short-term effects of non-surgical periodontal therapy on the circulating levels of interleukin-6 and C-reactive protein in patients with chronic periodontitis. J Indian Soc Periodontol. 2013; 17:36–41.

18. Li C, Lv Z, Shi Z, Zhu Y, Wu Y, Li L. Periodontal therapy for the management of cardiovascular disease in patients with chronic periodontitis. Cochrane Database Syst Rev. 2014; Cd009197.

19. D'Aiuto F, Nibali L, Parkar M, Suvan J, Tonetti MS. Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res. 2005; 84:269–273.

20. Bolerázska B, Mareková M, Markovská N. Trends in laboratory diagnostic methods in periodontology. Acta Medica (Hradec Kralove). 2016; 59:3–9.

21. Ram VS, Parthiban , Sudhakar U, Mithradas N, Prabhakar R. Bonebiomarkers in periodontal disease: a review article. J Clin Diagn Res. 2015; 9:Ze07–Ze10.

22. Salazar MG, Jehmlich N, Murr A, Dhople VM, Holtfreter B, Hammer E, et al. Identification of periodontitis associated changes in the proteome of whole human saliva by mass spectrometric analysis. J Clin Periodontol. 2013; 40:825–832.

23. Mahendra L, Mahendra J, Borra SK, Nagarajan A. Estimation of salivary neopterin in chronic periodontitis. Indian J Dent Res. 2014; 25:794–796.

24. Arjunkumar R, Sudhakar U, Jayakumar P, Arunachalam L, Suresh S, Virupapuram P. Comparative analysis of gingival crevicular fluid neopterin levels in health and periodontal disease: a biochemical study. Indian J Dent Res. 2013; 24:582–586.

25. Suri V, Suri V. Menopause and oral health. J Midlife Health. 2014; 5:115–120.

26. Dutt P, Chaudhary S, Kumar P. Oral health and menopause: a comprehensive review on current knowledge and associated dental management. Ann Med Health Sci Res. 2013; 3:320–323.

27. Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Update. 2005; 11:411–423.

28. Bolego C, Cignarella A, Staels B, Chinetti-Gbaguidi G. Macrophage function and polarization in cardiovascular disease: a role of estrogen signaling? Arterioscler Thromb Vasc Biol. 2013; 33:1127–1134.

29. Villa A, Rizzi N, Vegeto E, Ciana P, Maggi A. Estrogen accelerates the resolution of inflammation in macrophagic cells. Sci Rep. 2015; 5:15224.

30. Toniolo A, Fadini GP, Tedesco S, Cappellari R, Vegeto E, Maggi A, et al. Alternative activation of human macrophages is rescued by estrogen treatment in vitro and impaired by menopausal status. J Clin Endocrinol Metab. 2015; 100:E50–E58.

31. Novella S, Heras M, Hermenegildo C, Dantas AP. Effects of estrogen on vascular inflammation: a matter of timing. Arterioscler Thromb Vasc Biol. 2012; 32:2035–2042.

32. Acharya AB, Thakur S, Muddapur MV. Effect of scaling and root planing on serum interleukin-10 levels and glycemic control in chronic periodontitis and type 2 diabetes mellitus. J Indian Soc Periodontol. 2015; 19:188–193.

33. Ozmeric N, Baydar T, Bodur A, Engin AB, Uraz A, Eren K, et al. Level of neopterin, a marker of immune cell activation in gingival crevicular fluid, saliva, and urine in patients with aggressive periodontitis. J Periodontol. 2002; 73:720–725.

34. Pradeep AR, Kumar MS, Ramachandraprasad MV, Shikha C. Gingival crevicular fluid levels of neopterin in healthy subjects and in patients with different periodontal diseases. J Periodontol. 2007; 78:1962–1967.

35. Roitt IM, Brostoff J, Male DK. Immunology. 4th ed. London, UK: Mosby;1996.

36. Cortran RS, Kumar V, Robbins SL. Inflammation and repair. In : Cotran RS, Kumar V, Robbins SL, editors. Robbins' pathologic basis of disease. 5th ed. Philadelphia, PA: W.B. Saunders;1994. p. 51–92.

37. Schobersberger W, Hoffmann G, Grote J, Wachter H, Fuchs D. Induction of inducible nitric oxide synthase expression by neopterin in vascular smooth muscle cells. FEBS Lett. 1995; 377:461–464.

38. Flannagan RS, Heit B, Heinrichs DE. Antimicrobial mechanisms of macrophages and the immune evasion strategies of staphylococcus aureus. Pathogens. 2015; 4:826–868.

39. Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988; 157:87–94.