Chlorhexidine in Dentistry Part I: Functional Mechanism and Adverse Effects

Main Article Content

Supontep Teerakanok

Abstract

Since periodontal diseases and dental caries are mainly caused by oral microcosms, the elimination of oral biofilm plays a major in preventing and slowing disease progression. The use of antiseptic agents is another effective choice of treatment to reduce the number of oral microbes. Chlorhexidine is an antiseptic with a broad spectrum. Due to its high safety, chlorhexidine has been used widely in dentistry. This review article aimed to elucidate the mechanism of action against oral microbes, mechanism of controlling oral biofilm formation, adverse effects after using chlorhexidine in terms of cellular and clinical level.

Article Details

How to Cite
1.
Teerakanok S. Chlorhexidine in Dentistry Part I: Functional Mechanism and Adverse Effects. Khon Kaen Dent J [Internet]. 2020 Dec. 16 [cited 2024 Dec. 22];23(3):99-107. Available from: https://he01.tci-thaijo.org/index.php/KDJ/article/view/243604
Section
Review Article
Share |

References

Davies GE, Francis J, Martin AR, Rose FL, Swain G. 1:6-Di-4’-chlorophenyldiguanidohexane(hibitane);laboratory investigation of a new antibacterial agent of high potency. Br J Pharmacol Chemother 1954;9(2):192–6.

Löe H, Schiøtt CR. The effect of mouthrinses and topical application of chlorhexidine on the development of dental plaque and gingivitis in man. J Periodontal Res 1970; 5(2):79-83.

Schiøtt CR. Effect of chlorhexidine on the microflora of the oral cavity. J Periodontal Res Suppl 1973;12:7-10.

Wade WG, Addy M. In vitro activity of a chlorhexidine–containing mouthwash against subgingival bacteria. J Periodontol 1989;60(9):521-5.

Denton GW. Chlorhexidine. In: Block SS, editor. Disinfection, sterilization and preservation. 4thed. Philadelphia: Lea & Febiger, 1991:274-89.

Oosterwaal PJM, Mikx FHM, van den Brink ME, Renggli HH. Bactericidal concentrations of chlorhexidine‐digluconate, amine fluoride gel and stannous fluoride gel for subgingival bacteria tested in serum at short contact times. J Periodontal Res 1989;24(2):155-60.

Gilbert P, Moore LE. Cationic antiseptics: Diversity of action under a common epithet. J Appl Microbiol 2005;99(4):703-15.

Hugo WB, Longworth AR. Some aspects of the mode of action of chlorhexidine. J Pharm Pharmacol 1964;16: 655-62.

Hugo WB, Longworth AR. Cytological aspects of the mode of action of chlorhexidine diacetate. J Pharm Pharmacol 1965;17:28-32.

Hugo WB, Longworth AR. The effect of chlorhexidine on the electrophoretic mobility, cytoplasmic constituents, dehydrogenase activity and cell walls of Escherichia coli and Staphylococcus aureus. J Pharm Pharmacol 1966; 18(9):569-78.

Jones CG. Chlorhexidine: Is it still the gold standard? Periodontol 2000 1997;15:55-62.

Sonnenfeld EM, Beveridge TJ, Koch AL, Doyle RJ. Asymmetric distribution of charge on the cell wall of Bacillus subtilis. J Bacteriol 1985;163(3):1167-71.

Kawai F, Shoda M, Harashima R, Sadaie Y, Hara H, Matsumoto K. Cardiolipin domains in Bacillus subtilis marburg membranes. J Bacteriol 2004;186(5):1475-83.

Nishibori A, Kusaka J, Hara H, Umeda M, Matsumoto K. Phosphatidylethanolamine domains and localization of phospholipid synthases in Bacillus subtilis membranes. J Bacteriol 2005;187(6):2163-74.

Cheung HY, Wong MMK, Cheung SH, Liang LY, Lam YW, Chiu SK. Differential actions of chlorhexidine on the cell wall of bacillus subtilis and escherichia coli. PLoS One 2012;7(5):e36659.

Grenier D. Effect of chlorhexidine on the adherence properties of Porphyromonas gingivalis. J Clin Periodontol 1996;23(2):140-2.

Grenier D. Reduction of proteolytic degradation by chlorhexidine. J Dent Res 1993;72(3):630-3.

Scheie AA, Kjeilen JC. Effects of chlorhexidine, NaF and SnF2 on glucan formation by salivary and culture supernatant GTF adsorbed to hydroxyapatite. Scand J Dent Res 1987;95(6):532-5.

Rölla G, Löe H, Schiøtt CR. The affinity of chlorhexidine for hydroxyapatite and salivary mucins. J Periodontal Res 1970;5(2):90-5.

Rølla G, Løe H, Schiøtt CR. Retention of chlorhexidine in the human oral cavity. Arch Oral Biol 1971;16(9):1109-16.

Gjermo P, Bonesvoll P, Rölla G. Relationship between plaque-inhibiting effect and retention of chlorhexidine in the human oral cavity. Arch Oral Biol 1974;19(11):1031-4.

Bonesvoll P, Lökken P, Rölla G, Paus PN. Retention of chlorhexidine in the human oral cavity after mouth rinses. Arch Oral Biol 1974;19(3):209-12.

Bonesvoll P, Olsen I. Influence of teeth, plaque and dentures on the retention of chlorhexidine in the human oral cavity. J Clin Periodontol 1974;1(4):214-21.

Rölla G, Melsen B. On the mechanism of the plaque inhibition by chlorhexidine. J Dent Res 1975;54:B57-62.

Van Strydonck DAC, Timmerman MF, Van Der Velden U, Van Der Weijden GA. Plaque inhibition of two commercially available chlorhexidine mouthrinses. J Clin Periodontol 2005;32(3):305-9.

Supranoto SC, Slot DE, Addy MA, Van der Weijden GA. The effect of chlorhexidine dentifrice or gel versus chlorhexidine mouthwash on plaque, gingivitis, bleeding and tooth discoloration: a systematic review. Int J Dent Hyg 2015;13(2):83-92.

Haydari M, Bardakci AG, Koldsland OC, Aass AM, Sandvik L, Preus HR. Comparing the effect of 0.06% -, 0.12% and 0.2% Chlorhexidine on plaque, bleeding and side effects in an experimental gingivitis model: A parallel group, double masked randomized clinical trial. BMC Oral Health 2017;17(1):118.

Winrow MJ. Metabolic studies with radiolabelled chlorhexidine in animals and man. J Periodontal Res Suppl 1973;12:45-8.

Foulkes DM. Some toxicological observations on chlorhexidine. J Periodontal Res Suppl 1973;12:55-7.

Eley BM. Antibacterial agents in the control of supragingival plaque-a review. Br Dent J 1999;186(6): 286-96.

Lucarotti ME, White H, Deas J, Silver IA, Leaper DJ. Antiseptic toxicity to breast carcinoma in tissue culture: an adjuvant to conservation therapy? Ann R Coll Surg Engl 1990;72(6):388-92.

Babich H, Wurzburger BJ, Rubin YL, Sinensky MC, Blau L. An in vitro study on the cytotoxicity of chlorhexidine digluconate to human gingival cells. Cell Biol Toxicol 1995;11(2):79-88.

Bonacorsi C, Raddi MSG, Carlos IZ. Cytotoxicity of chlorhexidine digluconate to murine macrophages and its effect on hydrogen peroxide and nitric oxide induction. Brazilian J Med Biol Res 2004;37(2):207-12.

Hidalgo E, Dominguez C. Mechanisms underlying chlorhexidine-induced cytotoxicity. Toxicol In Vitro 2001;15(4-5):271-6.

Giannelli M, Chellini F, Margheri M, Tonelli P, Tani A. Effect of chlorhexidine digluconate on different cell types: A molecular and ultrastructural investigation. Toxicol In Vitro 2008;22(2):308-17.

Goldschmidt P, Cogen R, Taubman S. Cytopathologic effects of chlorhexidine on human cells. J Periodontol 1977;48(4):212-5.

Pucher JJ, Daniel JC. The effects of chlorhexidine digluconate on human fibroblasts in vitro. J Periodontol 1992;63(6):526-32.

Ribeiro DA, Bazo AP, da Silva Franchi CA, Marques MEA, Salvadori DMF. Chlorhexidine induces DNA damage in rat peripheral leukocytes and oral mucosal cells. J Periodontal Res 2004;39(5):358-61.

Knuuttila M, Söderling E. Effect of chlorhexidine on the release of lysosomal enzymes from cultured macrophages. Acta Odontol Scand 1981;39(5):285-9.

Vörös P, Dobrindt O, Perka C, Windisch C, Matziolis G, Röhner E. Human osteoblast damage after antiseptic treatment. Int Orthop 2014;38(1):177-82.

Faria G, Celes MRN, De Rossi A, Silva LAB, Silva JS, Rossi MA. Evaluation of chlorhexidine toxicity injected in the paw of mice and added to cultured L929 fibroblasts. J Endod 2007;33(6):715-22.

Gendron R, Grenier D, Sorsa T, Mayrand D. Inhibition of the activities of matrix metalloproteinases 2, 8, and 9 by chlorhexidine. Clin Diagn Lab Immunol 1999;6(3):437-9.

Cline NV, Layman DL. The effects of chlorhexidine on the attachment and growth of cultured human periodontal cells. J Periodontol 1992;63(7):598-602.

James P, Worthington HV, Parnell C, Harding M, Lamont T, Cheung A, et al. Chlorhexidine mouthrinse as an adjunctive treatment for gingival health. Cochrane Database Syst Rev 2017;3(3):CD0008676.

González C, Forner L, Llena C, Lozano A. Temperature changes in 2% chlorhexidine gluconate using two activation methods with different intensity levels. J Clin Exp Dent 2018;10(5):e458-61.

Gjermo P, Rølla G, Årskaug L. Effect on dental plaque formation and some in vitro properties of 12 bis-biguanides. J Periodontal Res Suppl 1973;12:81-92.

Eriksen HM, Nordbø H, Kantanen H, Elungsen JE. Chemical plaque control and extrinsic tooth discoloration: A review of possible mechanisms. J Clin Periodontol 1985;12(5):345-50.

Warner RR, Myers MC, Burns J, Mitra S. Analytical electron microscopy of chlorhexidine‐induced tooth stain in humans: direct evidence for metal‐induced stain. J Periodontal Res 1993;28(4):255-65.

Watts A, Addy M. Tooth discolouration and staining: a review of the literature. Br Dent J 2001;190(6):309-16.

Addy M, Moran J, Newcombe R, Warren P. The comparative tea staining potential of phenolic, chlorhexidine and anti‐adhesive mouthrinses. J Clin Periodontol 1995;22(12):923-8.

Raszewski Z, Nowakowska-Toporowska A, Wezgowiec J, Nowakowska D. Design and characteristics of new experimental chlorhexidine dental gels with anti-staining properties. Adv Clin Exp Med 2019;28(7):885-90.

Plantinga NL, Wittekamp BHJ, Leleu K, Depydt P, Van den Abeele AM, Brun-Buisson C, et al. Oral mucosal adverse events with chlorhexidine 2 % mouthwash in ICU. Intensive Care Med 2016;42(4):620-1.

Van der Weijden GA, Ten Heggeler JM, Slot DE, Rosema NA, Van der Velden U. Parotid gland swelling following mouthrinse use. Int J Dent Hyg 2010;8(4):276-9.

Eden BDS. Prevention strategies for periodontal diseases. In: Cappelli DP, Mobley CC, editors. Prevention in clinical oral health care. 1sted. Missouri: Mosby, 2008:213-9.

Lang NP, Catalanotto FA, Knöpfli RU, Antczak AA. Quality‐specific taste impairment following the application of chlorhexidine digluconate mouthrinses. J Clin Periodontol 1988;15(1):43-8.

Addy M. Oral hygiene products: potential for harm to oral and systemic health? Periodontol 2000 2008;48:54–65.

Fernandes M, Lourenço T, Lopes A, Spínola Santos A, Pereira Santos MC, Pereira Barbosa M. Chlorhexidine: a hidden life-threatening allergen. Asia Pac Allergy 2019;9(4):e29.

Opstrup MS, Jemec GBE, Garvey LH. Chlorhexidine allergy: on the rise and often overlooked. Curr Allergy Asthma Rep 2019;19(5):23.