The Influence of Hyaluronic Acid Adjunctive Therapy of Periodontitis on Salivary Markers of Oxidative Stress: Randomized, Controlled Clinical Trial

Iwona Olszewska-Czyz, Kristina Kralik, Marin Tota, Jelena Prpic, Iwona Olszewska-Czyz, Kristina Kralik, Marin Tota, Jelena Prpic

Abstract

Periodontitis is a common oral disease affecting the tooth-supporting tissues. Bacteria have been long viewed as the main causative factor in its development; however, many investigations have proved that aberrant immune and inflammatory response and the resulting misbalance between the damage caused by reactive oxygen species and the antioxidant capacity of tissues may be an underlying factor in disease progression that reduces healing potential. The objective of the current trial is to assess the outcomes of the addition of hyaluronic acid (HA) to standard non-surgical periodontal therapy (NST) on some major oxidative stress markers in saliva. HA-based gel designed for dental application was used and the measurements were taken after 3 months. HA adjunctive therapy had a significantly greater increase in markers with antioxidant properties as well as total antioxidant capacity compared to standard NST alone. Furthermore, clinically measured levels of gingival inflammation (bleeding on probing-BOP) and periodontal destruction (clinical attachment loss-CAL) were significantly correlated with these markers, and the correlation was negative. This investigation demonstrates that HA may indeed express antioxidant properties and improve the antioxidant capacity of periodontal tissues, thus improving the prognosis for the teeth and the results of periodontal therapy. Further investigations will be necessary to determine the duration of these effects over time.

Keywords: antioxidant status; oxidative stress; periodontitis.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT 2010 flow diagram.

References

    1. Petersen P.E., Ogawa H. The global burden of periodontal disease: Towards integration with chronic disease prevention and control. Periodontol. 2000;60:15–39. doi: 10.1111/j.1600-0757.2011.00425.x.
    1. Page R.C., Offenbacher S., Schroeder H.E., Seymour G.J., Kornman K.S. Advances in the pathogenesis of periodontitis: Summary of developments, clinical implications and future directions. Periodontol 2000. 2000;1997:216–248. doi: 10.1111/j.1600-0757.1997.tb00199.x.
    1. Feng Z., Weinberg A. Role of bacteria in health and disease of periodontal tissues. Periodontol. 2000;40:50–76. doi: 10.1111/j.1600-0757.2005.00148.x.
    1. Allen E.M., Matthews J.B., O’ Halloran D.J., Griffiths H.R., Chapple I.L. Oxidative and inflammatory status in Type 2 diabetes patients with periodontitis. J. Clin. Periodontol. 2011;38:894–901. doi: 10.1111/j.1600-051X.2011.01764.x.
    1. Cheng Z., Meade J., Mankia K., Emery P., Devine D.A. Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol. 2017;31:19–30. doi: 10.1016/j.berh.2017.08.001.
    1. Buczko P., Zalewska A., Szarmach I. Saliva and oxidative stress in oral cavity and in some systemic disorders. J. Physiol. Pharmacol. 2015;66:3–9.
    1. Carcuac O., Berglundh T. Composition of human peri-implantitis and periodontitis lesions. J. Dent. Res. 2014;93:1083–1088. doi: 10.1177/0022034514551754.
    1. Wang G.P. Defining functional signatures of dysbiosis in periodontitis progression. Genome Med. 2015;7:40. doi: 10.1186/s13073-015-0165-z.
    1. Fine N., Hassanpour S., Borenstein A., Sima C., Oveisi M., Scholey J., Cherney D., Glogauer M. Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States. J. Dent. Res. 2016;95:931–938. doi: 10.1177/0022034516645564.
    1. Baňasová L., Kamodyová N., Janšáková K., Tóthová Ľ., Stanko P., Turňa J., Celec P. Salivary DNA and markers of oxidative stress in patients with chronic periodontitis. Clin. Oral. Investig. 2015;19:201–207. doi: 10.1007/s00784-014-1236-z.
    1. Wang Y., Andrukhov O., Rausch-Fan X. Oxidative Stress and Antioxidant System in Periodontitis. Front. Physiol. 2017;8:910. doi: 10.3389/fphys.2017.00910.
    1. Tóthová L., Kamodyová N., Červenka T., Celec P. Salivary markers of oxidative stress in oral diseases. Front. Cell Infect. Microbiol. 2015;5:73. doi: 10.3389/fcimb.2015.00073.
    1. Sanz M., Herrera D., Kebschull M., Chapple I., Jepsen S., Beglundh T., Sculean A., Tonetti M.S., EFP Workshop Participants and Methodological Consultants Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline. J. Clin. Periodontol. 2020;47((Suppl. S22)):4–60. doi: 10.1111/jcpe.13290.
    1. Donos N., Calciolari E., Brusselaers N., Goldoni M., Bostanci N., Belibasakis G.N. The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic review of randomized, placebo-controlled clinical studies. J. Clin. Periodontol. 2020;47((Suppl. S22)):199–238. doi: 10.1111/jcpe.13232.
    1. Azzi A. Antioxidants: Wonder drugs or quackery? Biofactors. 2017;43:785–788. doi: 10.1002/biof.1388.
    1. Olszewska-Czyz I., Kralik K., Prpic J. Biomolecules in Dental Applications: Randomized, Controlled Clinical Trial Evaluating the Influence of Hyaluronic Acid Adjunctive Therapy on Clinical Parameters of Moderate Periodontitis. Biomolecules. 2021;11:1491. doi: 10.3390/biom11101491.
    1. Pilloni A., Zeza B., Kuis D., Vrazic D., Domic T., Olszewska-Czyz I., Popova C., Kotsilkov K., Firkova E., Dermendzieva Y., et al. Treatment of Residual Periodontal Pockets Using a Hyaluronic Acid-Based Gel: A 12 Month Multicenter Randomized Triple-Blinded Clinical Trial. Antibiotics. 2021;10:924. doi: 10.3390/antibiotics10080924.
    1. Urbaniak G.C., Plous S. Research Randomizer (Version 4.0) [Computer software] [(accessed on 9 October 2020)]. Available online: .
    1. Papapanou P.N., Sanz M., Buduneli N., Dietrich T., Feres M., Fine D.H., Flemmig T.F., Garcia R., Giannobile W.V., Graziani F., et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Clin. Periodontol. 2018;45((Suppl. S20)):S162–S170. doi: 10.1111/jcpe.12946.
    1. Tonetti M.S., Sanz M. Implementation of the new classification of periodontal diseases: Decision-making algorithms for clinical practice and education. J. Clin. Periodontol. 2019;46:398–405. doi: 10.1111/jcpe.13104.
    1. Lange D.E., Plagmann H.C., Eenboom A., Promesberger A. Klinische Bewertungsverahren zur Objektivierung der Mundhygiene Clinical methods for the objective evaluation of oral hygiene. Dtsch. Zahnarztl. Z. 1977;32:44–47.
    1. Ainamo J., Bay I. Problems and proposals for recording gingivitis and plaque. Int. Dent. J. 1975;25:229–235.
    1. Haas A.N., Furlaneto F., Gaio E.J., Gomes S.C., Palioto D.B., Castilho R.M., Sanz M., Messora M.R. New tendencies in non-surgical periodontal therapy. Braz, Oral Res. 2021;35((Suppl. S2)):e095. doi: 10.1590/1807-3107bor-2021.vol35.0095.
    1. Benzie I.F.F., Strain J.J. The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: The FRAP assay. Anal. Biochem. 1996;239:70–76. doi: 10.1006/abio.1996.0292.
    1. Beutler E., Duron O., Kelly B.M. Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 1963;61:882–888.
    1. Delides A., Spooner R.J., Goldberg D.M., Neal F.E. An optimized semi-automatic rate method for serum glutathione reductase activity and its application to patients with malignant disease. J. Clin. Pathol. 1976;29:73–77. doi: 10.1136/jcp.29.1.73.
    1. Fraisse L., Bonnet M.C., de Farcy J.P., Agut C., Dersigny D., Bayol A. A colorimetric 96-well microtiter plate assay for the determination of urate oxidase activity and its kinetic parameters. Anal. Biochem. 2002;309:173–179. doi: 10.1016/S0003-2697(02)00293-2.
    1. Sies H., Berndt C., Jones D.P. Oxidative Stress. Annu. Rev. Biochem. 2017;86:715–748. doi: 10.1146/annurev-biochem-061516-045037.
    1. Shapira L., Borinski R., Sela M.N., Soskolne A. Superoxide formation and chemiluminescence of peripheral polymorphonuclear leukocytes in rapidly progressive periodontitis patients. J. Clin. Periodontol. 1991;18:44–48. doi: 10.1111/j.1600-051X.1991.tb01118.x.
    1. Chapple I.L. Reactive oxygen species and antioxidants in inflammatory diseases. J. Clin. Periodontol. 1997;24:287–296. doi: 10.1111/j.1600-051X.1997.tb00760.x.
    1. Tóthová L., Celec P. Oxidative Stress and Antioxidants in the Diagnosis and Therapy of Periodontitis. Front. Physiol. 2017;8:1055. doi: 10.3389/fphys.2017.01055.
    1. Liu Z., Liu Y., Song Y., Zhang X., Wang S., Wang Z. Systemic oxidative stress biomarkers in chronic periodontitis: A meta-analysis. Dis. Mark. 2014;2014:931083. doi: 10.1155/2014/931083.
    1. Zhang L., Wang X., Cueto R., Effi C., Zhang Y., Tan H., Qin X., Ji Y., Yang X., Wang H. Biochemical basis and metabolic interplay of redox regulation. Redox Biol. 2019;26:101284. doi: 10.1016/j.redox.2019.101284.
    1. Abou Sulaiman A.E., Shehadeh R.M. Assessment of total antioxidant capacity (TAC) and the use of vitamin C in the treatment of non-smokers with chronic periodontitis. J. Periodontol. 2010;81:1547–1554. doi: 10.1902/jop.2010.100173.
    1. Chandra R.V., Srinivas G., Reddy A.A., Reddy B.H., Reddy C., Nagarajan S., Naveen A. Locally delivered antioxidant gel as an adjunct to nonsurgical therapy improves measures of oxidative stress and periodontal disease. J. Periodontal Implant Sci. 2013;43:121–129. doi: 10.5051/jpis.2013.43.3.121.
    1. Singh N., Chander Narula S., Kumar Sharma R., Tewari S., Kumar Sehgal P. Vitamin E supplementation, superoxide dismutase status, and outcome of scaling and root planing in patients with chronic periodontitis: A randomized clinical trial. J. Periodontol. 2014;85:242–249. doi: 10.1902/jop.2013.120727.
    1. Zare Javid A., Seal C.J., Heasman P., Moynihan P.J. Impact of a customised dietary intervention on antioxidant status, dietary intakes and periodontal indices in patients with adult periodontitis. J. Hum. Nutr. Diet. 2014;27:523–532. doi: 10.1111/jhn.12184.
    1. Domínguez A., Gómez C., García-Kass A.I., García-Nuñez J.A. IL-1beta, TNF-alpha, total antioxidant status and microbiological findings in chronic periodontitis treated with fluorescence-controlled Er: YAG laser radiation. Lasers Surg. Med. 2010;42:24–31. doi: 10.1002/lsm.20873.
    1. Muniz F.W., Nogueira S.B., Mendes F.L., Rösing C.K., Moreira M.M., de Andrade G.M., Carvalho Rde S. The impact of antioxidant agents complimentary to periodontal therapy on oxidative stress and periodontal outcomes: A systematic review. Arch. Oral Biol. 2015;60:1203–1214. doi: 10.1016/j.archoralbio.2015.05.007.
    1. Vernazza C., Heasman P., Gaunt F., Pennington M. How to measure the cost-effectiveness of periodontal treatments. Periodontol 2000. 2012;60:138–146. doi: 10.1111/j.1600-0757.2011.00406.x.
    1. Deas D.E., Moritz A.J., Sagun R.S., Gruwell S.F., Powell C.A. Scaling and root planing vs. conservative surgery in the treatment of chronic periodontitis. Periodontol. 2000;71:128–139. doi: 10.1111/prd.12114.
    1. Eliezer M., Imber J.C., Sculean A., Pandis N., Teich S. Hyaluronic acid as adjunctive to non-surgical and surgical periodontal therapy: A systematic review and meta-analysis. Clin. Oral Investig. 2019;23:3423–3435. doi: 10.1007/s00784-019-03012-w.
    1. Ke C., Sun L., Qiao D., Wang D., Zeng X. Antioxidant acitivity of low molecular weight hyaluronic acid. Food Chem. Toxicol. 2011;49:2670–2675. doi: 10.1016/j.fct.2011.07.020.
    1. Bergandi L., Skorokhod O.A., La Grotta R., Schwarzer E., Nuzzi R. Oxidative Stress, Lipid Peroxidation, and Loss of Hyaluronic Acid in the Human Vitreous Affected by Synchysis Scintillans. J. Ophthalmol. 2019;2019:7231015. doi: 10.1155/2019/7231015.
    1. Guentsch A., Preshaw P.M., Bremer-Streck S., Klinger G., Glockmann E., Sigusch B.W. Lipid peroxidation and antioxidant activity in saliva of periodontitis patients: Effect of smoking and periodontal treatment. Clin. Oral Investig. 2008;12:345–352. doi: 10.1007/s00784-008-0202-z.
    1. Koromantzos P.A., Makrilakis K., Dereka X., Offenbacher S., Katsilambros N., Vrotsos I.A., Madianos P.N. Effect of non-surgical periodontal therapy on C-reactive protein, oxidative stress, and matrix metalloproteinase (MMP)-9 and MMP-2 levels in patients with type 2 diabetes: A randomized controlled study. J. Periodontol. 2012;83:3–10. doi: 10.1902/jop.2011.110148.
    1. Arabacı T., Kermen E., Özkanlar S., Köse O., Kara A., Kızıldağ A., Duman Ş.B., Ibişoğlu E. Therapeutic Effects of Melatonin on Alveolar Bone Resorption after Experimental Periodontitis in Rats: A Biochemical and Immunohistochemical Study. J. Periodontol. 2015;86:874–881. doi: 10.1902/jop.2015.140599.
    1. Köse O., Arabaci T., Kizildag A., Erdemci B., Özkal Eminoğlu D., Gedikli S., Özkanlar S., Zihni M., Albayrak M., Kara A., et al. Melatonin prevents radiation-induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis. J. Periodontal Res. 2017;52:438–446. doi: 10.1111/jre.12409.

Source: PubMed

3
Abonnere