Abstract
Objectives
To compare the efficacy of N-acetyl cysteine (NAC) mouthwash with chlorhexidine (CHX) in prevention and treatment of experimental gingivitis
Materials and methods
Sixty subjects were assigned randomly and blindly into one of three equal groups: NAC, CHX, or placebo group. The study was conducted in two stages: preventive and treatment substudies. Professional prophylaxis was performed ahead of starting the preventive substudy. Then, the subjects were instructed to stop oral hygiene practices and begin rinsing twice/day with 15 ml of the assigned mouthwash (1.25% NAC, 0.2% CHX, or inert base). Plaque index (PI), gingival index (GI), and papillary bleeding index (PBI) were measured at baseline, 7, 14, and 21 days. The treatment substudy started on day 21 in which the subjects in the placebo group (now with established experimental gingivitis) were assigned to NAC (n = 10) or CHX (n = 10); the abovementioned indices were measured at 28 and 35 days. Efficacy of these interventions was compared.
Results
All groups accumulated plaque and developed some degree of gingivitis: full-blown in the placebo group and remarkably mild in the CHX group. NAC had slight preventive properties at days 14 and 21. In the treatment substudy, CHX was associated with remarkable reduction in plaque and gingivitis while NAC resulted in insignificant reductions.
Conclusions
1.25% NAC is marginally effective in prevention and treatment of experimental gingivitis.
Clinical relevance
When compared with the placebo, NAC showed promising preventive and treatment effects of gingivitis that deserve further development and studies.
Trial registration
ISRCTN31352091.
Similar content being viewed by others
References
Ciancio S (1992) Agents for the management of plaque and gingivitis. J Dent Res 71:1450–1454
Malhotra R, Grover V, Kapoor A, Saxena D (2011) Comparison of the effectiveness of a commercially available herbal mouthrinse with chlorhexidine gluconate at the clinical and patient level. J Indian Soc Periodontol 15:349–352. https://doi.org/10.4103/0972-124X.92567
Slots J (2002) Selection of antimicrobial agents in periodontal therapy. J Periodontal Res 37:389–398
Arunachalam LT, Sudhakar U, Vasanth J, Khumukchum S, Selvam VV (2017) Comparison of anti-plaque and anti-gingivitis effect of curcumin and chlorhexidine mouth rinse in the treatment of gingivitis: a clinical and biochemical study. J Indian Soc Periodontol 21:478–483. https://doi.org/10.4103/jisp.jisp_116_17
Goes P, Dutra CS, Lisboa MR, Gondim DV, Leitao R, Brito GA, Rego RO (2016) Clinical efficacy of a 1% Matricaria chamomile L. mouthwash and 0.12% chlorhexidine for gingivitis control in patients undergoing orthodontic treatment with fixed appliances. J Oral Sci 58:569–574. https://doi.org/10.2334/josnusd.16-0280
Mamgain P, Kandwal A, Mamgain RK (2016) Comparative evaluation of triphala and ela decoction with 0.2% chlorhexidine as mouthwash in the treatment of plaque-induced gingivitis and halitosis: a randomized controlled clinical trial. J Evid Based Complementary Altern Med 22:468–472. https://doi.org/10.1177/2156587216679532
Jones CG (1997) Chlorhexidine: is it still the gold standard? Periodontol 15:55–62
da Costa L, Amaral C, Barbirato DDS, Leao ATT, Fogacci MF (2017) Chlorhexidine mouthwash as an adjunct to mechanical therapy in chronic periodontitis: A meta-analysis. J Am Dent Assoc 148:308–318. https://doi.org/10.1016/j.adaj.2017.01.021
Rashed HT (2016) Evaluation of the effect of hydrogen peroxide as a mouthwash in comparison with chlorhexidine in chronic periodontitis patients: a clinical study. J Int Soc Prev Community Dent 6:206–212. https://doi.org/10.4103/2231-0762.183114
Berchier C, Slot D, Van der Weijden G (2010) The efficacy of 0.12% chlorhexidine mouthrinse compared with 0.2% on plaque accumulation and periodontal parameters: a systematic review. J Clin Periodontol 37:829–839. https://doi.org/10.1111/j.1600-051X.2010.01575.x
Duss C, Lang NP, Cosyn J, Persson GR (2010) A randomized, controlled clinical trial on the clinical, microbiological, and staining effects of a novel 0.05% chlorhexidine/herbal extract and a 0.1% chlorhexidine mouthrinse adjunct to periodontal surgery. J Clin Periodontol 37:988–997. https://doi.org/10.1111/j.1600-051X.2010.01609.x
Strydonck DA, Slot DE, Velden U, Weijden F (2012) Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review. J Clin Periodontol 39:1042–1055. https://doi.org/10.1111/j.1600-051X.2012.01883.x
Abdulrab S, Halboub E, Barngkgei I, Al-Hebshi N (2017) N-acetylcysteine as a candidate therapeutic for recurrent aphthous and aphthous-like ulcers. Dent Hypotheses 8:17–22. https://doi.org/10.4103/2155-8213.202028
Olofsson AC, Hermansson M, Elwing H (2003) N-acetyl-L-cysteine affects growth, extracellular polysaccharide production, and bacterial biofilm formation on solid surfaces. Appl Environ Microbiol 69:4814–4822. https://doi.org/10.1128/AEM.69.8.4814-4822.2003
Dinicola S, De Grazia S, Carlomagno G, Pintucci JP (2014) N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med Pharmacol Sci 18:2942–2948
Gocer H, Emir D, Onger ME, Dabak N (2017) Effects of bone cement loaded with teicoplanin, N-acetylcysteine or their combination on Staphylococcus aureus biofilm formation: an in vitro study. Eklem Hastalik Cerrahisi 28:13–18. https://doi.org/10.5606/ehc.2017.52507
Molina-Manso D, Del-Prado G, Gomez-Barrena E, Cordero-Ampuero J, Fernandez-Roblas R, Esteban J (2016) Effect of different agents with potential antibiofilm activity on antimicrobial susceptibility of biofilms formed by Staphylococcus spp. isolated from implant-related infections. J Antibiot (Tokyo) 69:686–688. https://doi.org/10.1038/ja.2016.9
Zhao T, Liu Y (2010) N-acetylcysteine inhibit biofilms produced by Pseudomonas aeruginosa. BMC Microbiol 10:140. https://doi.org/10.1186/1471-2180-10-140
Pollini S, Di Pilato V, Landini G, Di Maggio T, Cannatelli A, Sottotetti S, Cariani L, Aliberti S, Blasi F, Sergio F, Rossolini GM, Pallecchi L (2018) In vitro activity of N-acetylcysteine against Stenotrophomonas maltophilia and Burkholderia cepacia complex grown in planktonic phase and biofilm. PLoS One 13:e0203941. https://doi.org/10.1371/journal.pone.0203941
Cindy H-R, Rene H-D, Sergio G-R, Diana R-P, del Socorro FGM, Claudio C-R (2013) Rifampicin and N-acteylcisteyne inhibit oral bacterial growth and biofilm formation. Pharmaceut Innovat J 2:16–23. https://doi.org/10.1016/j.bjid.2016.08.010
Quah SY, Wu S, Lui JN, Sum CP, Tan KS (2012) N-acetylcysteine inhibits growth and eradicates biofilm of enterococcus faecalis. J Endod 38:81–85. https://doi.org/10.1016/j.joen.2011.10.004
Darrag AM (2013) Antimicrobial efficacy of endodontic irrigation solutions against planktonic microorganisms and dual-species biofilm. Tanta Dent J 10:129–137. https://doi.org/10.1016/j.tdj.2013.11.005
Moon JH, Jang EY, Shim KS, Lee JY (2015) In vitro effects of N-acetyl cysteine alone and in combination with antibiotics on Prevotella intermedia. J Microbiol 53:321–329. https://doi.org/10.1007/s12275-015-4500-2
Lee D, Kook S-H, Ji H, Lee S-A, Choi K-C, Lee K-Y, Lee J-C (2015) N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway. BMB Rep 48:636–641. https://doi.org/10.5483/BMBRep.2015.48.11.112
Orihuela-Campos RC, Tamaki N, Mukai R, Fukui M, Miki K, Terao J, Ito H-O (2015) Biological impacts of resveratrol, quercetin, and N-acetylcysteine on oxidative stress in human gingival fibroblasts. J Clin Biochem Nutr 56:220–227. https://doi.org/10.3164/jcbn.14-129
Toker H, Ozdemir H, Balcı H, Ozer H (2012) N-acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin-induced diabetic rats. J Periodontal Res 47:793–799. https://doi.org/10.1111/j.1600-0765.2012.01497.x
Alkadasi B, Abdulrab S, Gaafer S, Kalakonda B, Hosny M, Shaker O, Hosny M (2017) Effect of adjunctive use of systemic antioxidant therapy (N-acetylcysteine) on soluble receptor activator nuclear factor kappaB ligand levels in gingival crevicular fluid following surgical periodontal treatment for chronic periodontitis. J Oral Sci 59:519–526. https://doi.org/10.2334/josnusd.16-0701
Li W, Wang RE, Finger M, Lang NP (2014) Evaluation of the antigingivitis effect of a chlorhexidine mouthwash with or without an antidiscoloration system compared to placebo during experimental gingivitis. J Investig Clin Dent 5:15–22. https://doi.org/10.1111/jicd.12050
Trombelli L, Farina R, Silva CO, Tatakis DN (2018) Plaque-induced gingivitis: case definition and diagnostic considerations. J Periodontol 89(Suppl 1):S46–S73. https://doi.org/10.1002/JPER.17-0576
Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS (2018) Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol 89(Suppl 1):S173–S182. https://doi.org/10.1002/JPER.17-0721
Silness J, Löe H (1964) Periodontal disease in pregnancy II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 22:121–135
Löe H, Silness J (1963) Periodontal disease in pregnancy I. Prevalence and severity. Acta Odontol Scand 21:533–551
Saxer U and Mühlemann H (1975) Motivation and education. Schweizerische Monatsschrift fur Zahnheilkunde= Revue mensuelle suisse d’odonto-stomatologie 85:905–919
Löe H, Theilade E, Jensen SB (1965) Experimental gingivitis in man. J Periodontol 36:177–187
García V, Rioboo M, Serrano J, Herrera D, Sanz M (2011) Plaque inhibitory effect of a 0.05% cetyl-pyridinium chloride mouth-rinse in a 4-day non-brushing model. Int J Dent Hyg 9:266–273. https://doi.org/10.1111/j.1601-5037.2010.00490.x
Ulkur F, Arun T, Ozdemir F (2013) The effects of three different mouth rinses in a 4-day supragingival plaque regrowth study. Eur J Dent Educ 7:352–358. https://doi.org/10.4103/1305-7456.115420
Hu D, Li X, Sreenivasan PK, DeVizio W (2009) A randomized, double-blind clinical study to assess the antimicrobial effects of a cetylpyridinium chloride mouth rinse on dental plaque bacteria. Clin Ther 31:2540–2548. https://doi.org/10.1016/j.clinthera.2009.11.004
Solís C, Santos A, Nart J, Violant D (2011) 0.2% chlorhexidine mouthwash with an antidiscoloration system versus 0.2% chlorhexidine mouthwash: a prospective clinical comparative study. J Periodontol 82:80–85. https://doi.org/10.1902/jop.2010.100289
Lorenz K, Bruhn G, Heumann C, Netuschil L, Brecx M, Hoffmann T (2006) Effect of two new chlorhexidine mouthrinses on the development of dental plaque, gingivitis, and discolouration. A randomized, investigator-blind, placebo-controlled, 3-week experimental gingivitis study. J Clin Periodontol 33:561–567. https://doi.org/10.1111/j.1600-051X.2006.00946.x
Saxton C, Ouderaa F (1989) The effect of a dentifrice containing zinc citrate and triclosan on developing gingivitis. J Periodontal Res 24:75–80
Addy M, Mohan J (1983) Comparison of plaque accumulation after topical application and mouth rinsing with chlorhexidine gluconate. J Clin Periodontol 10:69–71
Davies R, Børglum Jensen S, Rindom Schiøtt C, Löe H (1970) The effect of topical application of chlorhexidine on the bacterial colonization of the teeth and gingiva. J Periodontal Res 5:96–101
Löe H, Rindom Schiøtt C (1970) The effect of mouthrinses and topical application of chlorhexidine on the development of dental plaque and gingivitis in man. J Periodontal Res 5:79–83
Wu M, Chen SW, Su WL, Zhu HY, Ouyang SY, Cao YT, Jiang SY (2016) Sex hormones enhance gingival inflammation without affecting IL-1beta and TNF-alpha in periodontally healthy women during pregnancy. Mediat Inflamm 2016:4897890. https://doi.org/10.1155/2016/4897890
Acknowledgements
The authors wish to thank Shiba-Pharma (Shiba-Pharmaceuticals & Chemicals Mfg. Co. Ltd., Yemen) for it is cooperation and manufacturing of research rinsing. They also thank the students of the University of Science and Technology, Sana’a, Yemen, who volunteered to participate in this study and for their dedication.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
“The study protocol was formally approved by the Research Ethics Committee at the Faculty of Medicine and Health Sciences, University of Sciences and Technology, Sana’a, Yemen (No 2016/20). The study has been conducted in full accordance with the World Medical Association Declaration of Helsinki.”
Informed consent
“A written informed consent was obtained from each of the participants.”
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Al-Kamel, A., Al-Hajj, W.A., Halboub, E. et al. N-acetyl cysteine versus chlorhexidine mouthwashes in prevention and treatment of experimental gingivitis: a randomized, triple-blind, placebo-controlled clinical trial. Clin Oral Invest 23, 3833–3842 (2019). https://doi.org/10.1007/s00784-019-02813-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00784-019-02813-3