Skip to main content

Evaluation of biochemical and clinical effects of hyaluronic acid on non-surgical periodontal treatment: a randomized controlled trial



Recent studies reported that hyaluronic acid (HA) has anti-inflammatory, anti-edematous, and anti-bacterial activities in dentistry, particularly in gingival disorders caused by subgingival plaque microorganisms.


This study aimed to evaluate the early term effects of HA as an adjunct to scaling and root planing (SRP) on clinical parameters, periodontal inflamed surface area (PISA), and adenosine deaminase (ADA), catalase (CAT), and glutathione (GSH) levels in gingival crevicular fluid (GCF) in periodontitis.


A total of 24 periodontitis patients per group were included in this randomized-controlled study. The study population was divided into four groups: in Group 1: SRP+ saline; in Group 2: SRP + HA gel; in Group 3: SRP+ HA mouth rinse; and in Group 4: SRP + HA mouth rinse + HA gingival gel were applied. At baseline and week 4, clinical parameters and PISA were calculated. Also, biochemicals’ (ADA, CAT, and GSH) levels were determined by spectrophotometric analysis.


There was a statistically significant improvement in clinical parameters and PISA in all four groups in control sessions (p < 0.05). There was a significant decrease in ADA in GCF and significant increases in CAT and GSH levels after SRP (p < 0.05) in all four groups. The groups that were administered only gel (2nd and 4th) were different from other groups in terms of ADA, CAT, and GSH levels at 1st week (p < 0.05).


HA application as an adjunct to SRP did not affect the clinical results, although, in the control sessions following the application, the results were favorable for the biochemical data in gel-applied groups.

Trial registration (NCT03754010)

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Tonetti MS, Greenwell H, Kornman KS (2018) Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol 89:159–172

    Google Scholar 

  2. 2.

    Nesse W, Abbas F, Van Der Ploeg I et al (2008) Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol 35(8):668–673

    PubMed  Google Scholar 

  3. 3.

    Cugini MA, Haffajee AD, Smith C et al (2000) The effect of scaling and root planing on the clinical and microbiological parameters of periodontal diseases: 12-month results. J Clin Periodontol 27(1):30–36

    CAS  PubMed  Google Scholar 

  4. 4.

    Jiang D, Liang J, Noble PW (2011) Hyaluronan as an immune regulator in human diseases. Physiol Rev 91(1):221–264

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Shimabukuro Y, Ichikawa T, Takayama S et al (2005) Fibroblast growth factor-2 regulates the synthesis of hyaluronan by human periodontal ligament cells. J Cell Physiol 203(3):557–563

    CAS  PubMed  Google Scholar 

  6. 6.

    Hakansson L, Hallgren R, Venge P (1980) Regulation of granulocyte function by hyaluronic acid: in vitro and in vivo effects on phagocytosis, locomotion, and metabolism. J Clin Invest 66(2):298–305

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Surdacka A, Stopa J (2005) The effect of xylitol tooth paste on the oral cavity environment. J Prev Med 13(1–2):98–107

    Google Scholar 

  8. 8.

    Dahiya P, Kamal R, Gupta R et al (2013) Reactive oxygen species in periodontitis. J Indian Soc Periodontol 17(4):411–416

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Matés JM, Sánchez-Jiménez F (1999) Antioxidant enzymes and their implications in pathophysiologic processes. Front Biosci 4:339–345

    Google Scholar 

  10. 10.

    Day BJ (2009) Catalase and glutathione peroxidase mimics. Biochem Pharmacol 77(3):285–296

    CAS  PubMed  Google Scholar 

  11. 11.

    Xia Y, Khatchikian G, Zweier JL (1996) Adenosine deaminase inhibition prevents free radical-mediated injury in the postischemic heart. J Biol Chem 271(17):10096–10102

    CAS  PubMed  Google Scholar 

  12. 12.

    Liao YJ, Wu CY, Lee SW et al (2012) Adenosine deaminase activity in tuberculous peritonitis among patients with underlying liver cirrhosis. World J Gastroenterol 18(37):5260–5265

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Dikensoy O, Namiduru M, Hocaoglu S et al (2002) Increased pleural fluid adenosine deaminase in brucellosis is difficult to differentiate from tuberculosis. Respiration 69(6):556–559

    PubMed  Google Scholar 

  14. 14.

    Giusti G (1974) Adenosine deaminase. In: Bergmeyer HI (ed) Methods of enzymatic analyses. Academic Press, New York, pp 1092–1098

    Google Scholar 

  15. 15.

    Aebi H, Bergmayer H (1974) Catalase. In: Bergmayer HU (ed) Methods of enzymatic analysis. Academic Press, pp 673–684

  16. 16.

    Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34(3):497–500

    CAS  PubMed  Google Scholar 

  17. 17.

    Eick S, Renatus A, Heinicke M et al (2013) Hyaluronic acid as an adjunct after scaling and root planing: a prospective randomized clinical trial. J Periodontol 84(7):941–949

    PubMed  Google Scholar 

  18. 18.

    Johannsen A, Tellefsen M, Wikesjö U, Johannsen G (2009) Local delivery of hyaluronan as an adjunct to scaling and root planing in the treatment of chronic periodontitis. J Periodontol 80(9):1493–1497

    CAS  PubMed  Google Scholar 

  19. 19.

    Rajan P, Baramappa R, Rao NM et al (2014) Hyaluronic acid as an adjunct to scaling and root planing in chronic periodontitis. A randomized clinical trail. J Clin Diagn Res 8(12):ZC11–ZC14

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Pilloni A, Annibali S, Dominici F et al (2011) Evaluation of the efficacy of an hyaluronic acid-based biogel on periodontal clinical parameters. A randomized-controlled clinical pilot study. Ann Stomatol (Roma) 2:3–9

    Google Scholar 

  21. 21.

    Mesa FL, Aneiros J, Cabrera A et al (2002) Antiproliferative effect of topic hyaluronic acid gel. Study in gingival biopsies of patients with periodontal disease. Histol Histopathol 17:747–753

    CAS  PubMed  Google Scholar 

  22. 22.

    Bevilacqua L, Eriani J, Serroni I et al (2012) Effectiveness of adjunctive subgingival administration of amino acids and sodium hyaluronate gel on clinical and immunological parameters in the treatment of chronic periodontitis. Ann Stomatol (Roma) 3(2):75–81

    Google Scholar 

  23. 23.

    Engström P-E, Shi X-Q, Tronje G et al (2001) The effect of hyaluronan on bone and soft tissue and immune response in wound healing. J Periodontol 72(9):1192–1200

    PubMed  Google Scholar 

  24. 24.

    Leira Y, Martín-Lancharro P, Blanco J (2018) Periodontal inflamed surface area and periodontal case definition classification. Acta Odontol Scand 76(3):195–198

    PubMed  Google Scholar 

  25. 25.

    Slot DE, Timmerman MF, Versteeg PA et al (2012) Adjunctive clinical effect of a water-cooled Nd:YAG laser in a periodontal maintenance care programme: a randomized controlled trial. J Clin Periodontol 39(12):1159–1165

    PubMed  Google Scholar 

  26. 26.

    Rosenberg DR, Andrade CX, Chaparro AP et al (2015) Short-term effects of 2% atorvastatin dentifrice as an adjunct to periodontal therapy: a randomized double- masked clinical trial. J Periodontol 86(5):623–630

    CAS  PubMed  Google Scholar 

  27. 27.

    Bertl K, Bruckmann C, Isberg P-E et al (2015) Hyaluronan in non-surgical and surgical periodontal therapy: a systematic review. J Clin Periodontol 42:236–246

    CAS  PubMed  Google Scholar 

  28. 28.

    Jentsch H, Pomowski R, Kundt G, Göcke R (2003) Treatment of gingivitis with hyaluronan. J Clin Periodontol 30:159–164

    CAS  PubMed  Google Scholar 

  29. 29.

    Pagnacco A, Vangelisti R, Erra CPA (1997) Double-blind clinical trial vs. placebo of a new sodium-hyaluro-nate-based gingival gel. Attual Ter Internazionale 15:1–7

    Google Scholar 

  30. 30.

    Pistorius A, Martin M, Willershausen B, Rockmann P (2005) The clinical application of hyaluronic acid in gingivitis therapy. Quintessence Int 36:531–538

    PubMed  Google Scholar 

  31. 31.

    Weigel PH, Fuller GM, LeBoeuf RD (1986) A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing. J Theor Biol 119(2):219–234

    CAS  PubMed  Google Scholar 

  32. 32.

    Trivedi S, Lal N (2017) Antioxidant enzymes in periodontitis. J Oral Biol Craniofacial Res 7(1):54–57

    Google Scholar 

  33. 33.

    Dede F, Dogan S, Balli U, Avcı B (2017) Relationship between gingival inflammation and total glutathione. J Turgut Ozal Med Cent 24(2):162–166

    Google Scholar 

  34. 34.

    Palwankar P, Rana M, Arora K, Deepthy C (2015) Evaluation of non-surgical therapy on glutathione levels in chronic periodontitis. Eur J Dent 9(3):415–422

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Dahiya P, Kamal R, Gupta R, Saini H (2016) Evaluation of the serum antioxidant status in patients with chronic periodontitis. Indian J Multidiscip Dent 6(1):3–6

    Google Scholar 

  36. 36.

    Hasko G, Kuhel DG, Nemeth ZH et al (2000) Inosine inhibits inflammatory cytokine production by a posttranscriptional mechanism and protects against endotoxin- induced shock. J Immunol 164:1013–1019

    CAS  PubMed  Google Scholar 

  37. 37.

    Sahin Aydinyurt H, Taskin C, Eskin K (2019) Comparison of adenosine deaminase and catalase activity of periodontally different diagnosed teeth in smokers. Van Sag Bil Derg 12(2):1–7

    Google Scholar 

  38. 38.

    Sarhat ER, Hamad AI, Mohammaed IJ, Sarhat TR (2018) The effect of diabetic patients with chronic periodontitis on serum paraoxonase, adenosine deaminase. Mustansiria Dent J 15:130–134

    Google Scholar 

  39. 39.

    Antonioli L, Colucci R, La Motta C et al (2012) Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Curr Drug Targets 13(6):842–862

    CAS  PubMed  Google Scholar 

  40. 40.

    Chauhan AS, Bains VK, Gupta V et al (2013) Comparative analysis of hyaluronan gel and xanthan-based chlorhexidine gel, as adjunct to scaling and root planing with scaling and root planning alone in the treatment of chronic periodontitis:a preliminary study. Contemp Clin Dent 4:54–61

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Chaves ES, Wood RC, Jones AA et al (1993) Relationship of “bleeding on probing” and “gingival index bleeding” as clinical parameters of gingival inflammation. J Clin Periodontol 20(2):139–143

    CAS  PubMed  Google Scholar 

  42. 42.

    Gharbi A, Hamila A, Bouguezzi A et al (2019) Biochemical parameters and oxidative stress markers in Tunisian patients with periodontal disease. BMC Oral Health 19:225

    PubMed  PubMed Central  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Hacer Sahin Aydinyurt.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Van Yuzuncu Yil University, Ethics Committee (Date/No. 19.07.2017/09).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Aydinyurt, H.S., Akbal, D., Altindal, D. et al. Evaluation of biochemical and clinical effects of hyaluronic acid on non-surgical periodontal treatment: a randomized controlled trial. Ir J Med Sci 189, 1485–1494 (2020).

Download citation


  • Hyaluronic acid
  • Periodontics
  • Periodontitis
  • Periodontal treatment