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Chlorhexidine: The gold standard antiplaque agent


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Chlorhexidine is one of the most widely and commonly used antiplaque and antigingivitis agent. The properties and mechanism of action of chlorhexidine must be understood in order to be put into maximum use. Chlorhexidine was used as a broad spectrum antiseptic since the 1950's. Its antibacterial action is due to the disruption of the bacterial cell membrane by the chlorhexidine molecules, increasing the permeability and resulting in cell lysis. It can be either bacteriostatic or bactericidal depending on the dose. It is available in different formulations. However it does have some side effects like permanent staining of teeth and dysgeusia. This article discusses the various clinical applications, properties and adverse effects of chlorhexidine.
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Chlorhexidine: The Gold Standard Antiplaque Agent
Shruti Balagopal1, Radhika Arjunkumar2
1Student,Saveetha Dental College, Chennai
2Senior Lecturer,Department of Periodontics
Saveetha Dental College, Chennai
Chlorhexidine is one of the most widely and commonly used antiplaque and antigingivitis agent. The properties and mechanism of action of
chlorhexidine must be understood in order to be put into maximum use. Chlorhexidine was used as a broad spectrum antiseptic since the
1950’s. Its antibacterial action is due to the disruption of the bacterial cell membrane by the chlorhexidine molecules, increasing the
permeability and resulting in cell lysis. It can be either bacteriostatic or bactericidal depending on the dose. It is available in different
formulations. However it does have some side effects like permanent staining of teeth and dysgeusia. This article discusses the various
clinical applications, properties and adverse effects of chlorhexidine.
Chlorhexidine, mouthrinse, chemical plaque control
Chlorhexidine is a gold standard against which other
antiplaque and antigingivitis agents are measured.
Understanding the properties and limitations of the molecule
can ensure that the efficacy of the agent is maximized and the
side effects are minimized allowing it to rightly remain the
gold standard.
Dental plaque
Dental plaque clinically is a structured resilient, grayish-
yellow substance that tenaciously adheres to the intraoral
hard surfaces including removable and fixed restorations [1].
Plaque control
It is the removal of microbial plaque and the prevention of its
accumulation on the tooth and adjacent gingival tissues to
prevent calculus formation. Plaque control can be of two
Mechanical plaque control
Chemical plaque control
Mechanical plaque control
Dental plaque is one of the most important etiological factors
in the onset of periodontal disease. Dental plaque mineralizes
to form dental calculus. Calculus formation is significantly
reduced by proper plaque control. Bacterial plaque can be
removed effectively by mechanical means. It is safe and
effective. The various methods include:
Interdental cleaning aids
Dental floss
Interdental brush and swab
Chemical plaque control
Antimicrobial agents: Chemicals that have a bacteriostatic or
bacteriocidal effect in vitro that alone cannot be extrapolated
to a proven efficacy in vivo against plaque.
Plaque reducing/inhibitory agents: Chemicals that have only
been shown to reduce the quantity and/or affect quality of
plaque which may or may not be sufficient to influence
gingivitis and/or caries.
Antiplaque agents: Chemicals that have an effect on plaque
sufficient to benefit gingivitis and/or caries.
Antigingivitis agents: Chemicals which reduce gingival
inflammation without necessarily influencing bacterial plaque
(includes anti-inflammatory agents).
Chemical plaque control agents [2]
The various chemical plaque control agents are listed in
Table 1.
Commercial mouthwashes can be classified into based on
their substantivity, range of antibacterial activity against
various plaque bacteria, possible anti inflammatory effect,
acceptable taste, ability to promote fresh mouth sensation.
They can also be classified as group A,B and C as follows,
Group A agents- antiplaque
Chlorhexidine, acidified sodium chlorate, salifluor and
Group B agents-plaque inhibitory
cetyl pyridinium chloride,
essential oil and triclosan rinses
used as adjuncts to mechanical cleaning
Group C agents-Have a low to moderate activity and
are used for cosmetic purposes like breath freshening
Sanguinarine , oxygenating agents, saturated pyrimidine,
Shruti Balagopal et al /J. Pharm. Sci. & Res. Vol.5(12), 2013, 270 - 274
Table 1- Chemical plaque control agents
Bisbiguanide antiseptics
Bisbiguanide compounds are a group of chemical plaque
control agents and comprises of the following agents
From a therapeutic point of view, the most obvious benefit of
using mouth rinses is the potential to reduce plaque and
gingivitis and particularly in youngsters where mechanical
plaque control is not optimal in maintaining gingival health.
The ADA council for scientific affairs has proposed a
program for acceptance of plaque control agents. These
include that the patients be evaluated in placebo control trials
of 6 months or longer and demonstrate significantly improved
gingival health compared with controls [3].
To date the ADA has accepted 2 agents for treatment of
gingivitis which include prescription solution of
chlorhexidine digluconate oral rinse and non prescription
essential oil rinse.
Chlorhexidine was developed by Imperial Chemical
Industries in England during 1940’s.It was marketed as a
general antiseptic in the year 1950. In 1957 chlorhexidine
was introduced for human use in Britain as an antiseptic for
skin. Later it was widely used in medicine and surgery.
Plaque inhibition first investigated by Schroeder in 1969[4]. A
definitive study for caries inhibition by inhibition of dental
plaque was done by Loe and Schiott 1972[5].
Chlorhexidine is available in various forms such as
digluconate, acetate and hydrochloride salts which are
sparingly soluble in water.
Chlorhexidine is a symmetrical molecule.It has four
chlorophenyl rings and two biguanide groups connected by a
central hexamethylene bridge. (figure 1)
Figure 1- Structure of chlorhexidine
Chlorhexidine is an antimicrobial agent. It acts on the inner
cytoplasmic membrane hence it is a membrane active type of
substance. It is dicationic at pH levels above 3.5. It prevents
plaque accumulation, hence it is a antiplaque and
antigingivitis agent[6] and reduces the adherence of
Porphyromonas gingivalis to epithelial cells[7]. It can be
bacteriostatic or bactericidal depending on the dose. It acts
against a wide array of bacteria including Gram positive and
Gram negative bacteria, dermatophytes and lipolytic viruses.
It also acts against fungi, yeasts and some viruses including
Hepatitis B virus and Human Immunodeficiency Virus. It
acts against Streptococcus mutants making it anticariogenic
in nature. Studies have also shown that chlorhexidine has the
ability to neutralize pathogenic agents such as Streptococcus
aureus, Porphyromans gingivalis and Prevotella intermedia.[8]
Another most important unique property of chlorhexidine is
its substantivity. Substantivity refers to the oral retentiveness.
It depends upon various factors such as concentration, pH,
temperature and time of contact of the solution with oral
Mechanism of action of chlorhexidine:
The mechanism of action of chlorhexidine is outlined in
table 2.
Enzymes Protease, Lipase, Nuclease, Dextranase, Mutanase, Glucoseoxidase, Amyloglucosidase
Bisbiguanides Chlorhexidine, Alexidene, Octenidine
Quaternary Ammonium
Compounds Cetyl pyridinium chloride, Benzalconium Chloride
Phenolic compounds Thymol, 4-Hexylresorcinol, 2-Phenylphenol Eucalyptol, Listerene
Fluorides Sodium fluoride, Sodium monofluorophosphate Stannous fluoride, Amine fluoride
Metal ions Copper, Zinc, Tin
Oxygenating agents Peroxides
Other Antiseptics Iodine, Povidone iodine, Chloramine-T Sodium hypochlorite, Hexetidine, Triclosan
Salifluor, Delmopinol
Shruti Balagopal et al /J. Pharm. Sci. & Res. Vol.5(12), 2013, 270 - 274
Table 2- Mechanism of action of chlorhexidine
Chlorhexidine mouth rinses are available in the form of 0.2%
and 0.12%.There is equal efficacy for 0.2%and 0.12% rinses
when used at appropriate similar doses [10]. The time of
rinsing is 30 or 60 seconds depending on the adsorption rate
of antiseptics to the oral surfaces (50% of chlorhexidine binds
to receptors within 15 seconds) but this does vary from
individual to individual. The plaque inhibiting effect of a
0.2%chlorhexidine with rinsing times of 15, 30 and 60
seconds following a 72 hour non brushing period showed no
difference [11]. The ideal regimen is twice daily (morning and
night) which will have a substantivity for 12 hours.
The addition of fluoride to chlorhexidine is considered
questionable [12]. The concentration of 0.06% and sodium
fluoride 0.2% and 0.055% of stannous fluoride was
considered compatible with fluoride [13]. The chlorhexidine
monofluorophosphate complexes was considered
incompatible without fluorides [14].
The different available concentrations of chlorhexidine gel
are 1%, 0.2%, 0.12%. They are delivered in trays and
toothbrushes. Chlorhexidine gel, that is applied once a day
has therapeutic effects, like reducing oral malodour and
also reduces chlorhexidine staining [15].
0.12% of chlorhexidine with 1 parts per million of fluoride
has antiplaque effects similar to chlorhexidine mouthwash.
However there were difficulties in incorporating
chlorhexidine into gels and toothpastes.1% chlorhexidine
used as slurries and rinsed twice per day for one minute
causes significant reduction in the plaque and gingival scores
but also causes stains. Chlorhexidine in dentifrices gained
little attention due to its possible interaction with anionic
ingredients contained in toothpaste and competition for oral
retention sites [16].
0.1% and0.2% sprays have similar plaque inhibition
properties of 0.2% mouthwash. It is well received by
physically and mentally handicapped patients [17].
Chlorhexidine varnishes are used for prophylaxis against root
caries [18].
Sugar free chewing gum
Chlorhexidine remains unbound in this form. It contains
20mg of chlorhexidine diacetate. It is advised to chew 2
The bacterial cell wall is negatively charged and contains sulphates and phosphates
Dicationic positively charged chlorhexidine is attracted to the negatively charged bacterial cell wall with specific and strong
adsorption to phosphate containing compounds
Alters the integrity of the bacterial cell membrane and chlorhexidine is attracted to the inner cell membrane
Chlorhexidine binds to the phospholipids in the inner membrane and there is leakage of low molecular weight compounds
like potassium ions
By increasing the concentration of chlorhexidine there is progressive damage to the membrane
There is coagulation and precipitation of the cytoplasm by the formation of phosphate complexes which include adenosine
triphosphate and nucleic acids
Cytoplasm of the cells are chemically precipitated
Bactericidal stage which is irreversible
Shruti Balagopal et al /J. Pharm. Sci. & Res. Vol.5(12), 2013, 270 - 274
pieces twice per day for 10 minutes. This procedure is said to
cause less stains. It is a good method of using chlorhexidine
for a long period of time [19].
It is used as an adjunct to oral hygiene and professional
prophylaxis. It is used post oral surgery in periodontal
surgery or root planing. Studies have shown that the daily use
of mouthrinse combined with toothbrushing resulted in
reduced interproximal plaque when compared with
toothbrushing and daily flossing [20]. Chlorhexidine is of
importance in the maintainance protocol in immediate
function implants as there is a correlation between plaque and
bleeding index revealed a good result for 0.2% chlorhexidine
gel for daily implant self care at 6 months [21]. It is used in
patients with intermaxillary fixation and in patients who are
under high risk of caries. For those patients who are
physically and mentally handicapped chlorhexidine sprays
can be used [22]. It is used in medically compromised patients
who are predisposed to oral candidiasis. Chlorhexidine is
used to limit the bacteremia and operatory contamination by
oral bacteria and as an adjunct to antibiotic prophylaxis.
Other uses of chlorhexidine include sub gingival irrigation,
management of denture stomatitis, hypersensitivity and for
oral malodour. Full mouth disinfection has been introduced
with scaling and root planing and the application of
chlorhexidine into periodontal pockets with daily use of
chlorhexidine rinses at home for 2 months [23]. Chlorhexidine
formulations have well proven short to medium term
application as adjuncts and even replacements for mechanical
cleaning but it is still controversial [24]. Wound healing is
enhanced when chlorhexidine rinses are used before
extractions and after scaling and root planing or periodontal
surgery [25]. Chlorhexidine is shown to induce changes to
human gingival fibroblast collagen production and non
collagen protein production [26]. There is 65% reduction in
collagen production and a 75% reduction in non collagen
protein production.
Halita is the name of a mouth rinse containing 0.05% of
chlorhexidine, 0.05% cetyl pyridinium chloride and 0.14% of
zinc lactate. It is used in the management of halitosis [27, 28].
Zinc is added as it has the ability to convert volatile sulfur
compounds and it also acts synergistically with
chlorhexidine. Other clinical benefits include its use as a root
canal irrigant [29] and in atraumatic restorative treatment
where chlorhexidine containing glass ionomer cement [30].
Chlorhexidine is also used for surgical skin preparation for
the patient and the surgeon. Chlorhexidine is used as a local
drug delivery system in the form of a bio-degradable chip to
be used in the subgingival environment [31]. There is
controlled delivery of chlorhexidine to the periodontal
pocket. A slow sub-gingival release of 2.5mg of
chlorhexidine is found to have an average drug concentration
greater than 125 microgram per milliliter for 7 to 10 days.
The concentration of the drug remains above the minimum
inhibitory concentration for more than 99% of the
subgingival micro-organisms from the periodontal pockets.
The results of several clinical trials have shown that the use
of the chlorhexidine chip in conjunction with scaling and root
planing is effective in reducing periodontitis, clinical
attachment loss and bleeding on probing over a period of 6 to
9 months. The use of the controlled release of chlorhexidine
delivery system during maintenance therapy allows greater
improvement in clinical signs of periodontitis. In subgingival
exudates, the serum proteins may effectively compete with
the bacteria for the chlorhexidine, thus reducing the
availability of the drug. This might account for the occasional
lack of clinical effectiveness when the agent is administered
subgingivally [32].
Toxicology and side effects [33]
The side effects of chlorhexidine include brown
discolouration of the teeth, restorative materials and dorsum
of tongue. There is taste perturbation. There can be oral
mucosal erosion which is an idiosyncratic reaction and is
dose dependent. The bitter taste is difficult to mask.
Chlorhexidine staining
There is degradation of the chlorhexidine molecule to release
parachloroaniline. Non enzymatic browning reactions take
place called catalysis of Maillard. Protein denaturation and
metal sulfide formation occurs and there is precipitation of
anionic dietry chromogens [34].
Metabolism of chlorhexidine
The chlorhexidine that is swallowed undergoes minimal
metabolic changes. It has a half life of 4 days and it is
excreted in faeces.
Safety of chlorhexidine
Chlorhexidine is poorly absorbed in the gut and displays very
low toxicity. It does not cause any teratogenic alterations.
There is no evidence of formation of carcinogenic substances.
After the use of chlorhexidine mouthwash the intake of tea,
coffee and red wine must be avoided. The usage is restricted
in cases of anterior composite restorations and glass ionomer
restorations. There should be a 30 minute lapse between the
usage of a dentifrice and chlorhexidine mouth wash [35]. It is
so advised because the toothpastes contain detergents which
are predominantly anionic agents. Chlorhexidine molecule
being dicationic tends to bind with the anionic agents leading
to a reduction in the substantivity of chlorhexidine
Comparative studies
Increasing the rinsing frequency of cetyl pyridinium chloride
to four times a day has been suggested to produce efficacy
equivalent to that of chlorhexidine [8]. Listerine has a
moderate plaque inhibitory effect poor oral retention and
some antigingivitis effects [36]. Substantivity of hexitidine
is one to three hours and has some plaque inhibitory effects
[37]. The effect of three commercial mouth rinses on cultured
human gingival fibroblast, an in vitro study revealed that
chlorhexidine, listerine and povidone iodine are capable of
inducing a dose dependant reduction in cellular proliferation
of fibroblasts [38].
Shruti Balagopal et al /J. Pharm. Sci. & Res. Vol.5(12), 2013, 270 - 274
Chronic periodontitis is always preceded by chronic
gingivitis; chemicals that inhibit plaque may be expected to
be of value in both the prevention and management of
periodontal disease in some individuals. Thus, the use of a
chemical plaque-inhibitory mouthwash as an adjunct to tooth
brushing may have a major effect on improving the oral
health of the individual. Chlorhexidine is one chemical
plaque control agent which has various clinical applications
in dentistry especially in Periodontics . Chlorhexidine in its
various formulations has come to stay and it is appropriate to
call it the gold standard chemical plaque control agent.
1. Beck JD, Koch GG, Rosier RG, Tudor GE; Prevalence and risk
indicators for periodontal attachment loss in population of older
community-dwelling blacks and whites, J Periodontol 1971;61:521
2. Addy et al Chlorhexidine digluconate–an agent for chemical plaque
control and prevention of gingival inflammation: J Periodont res 1986;
21:16 74-89.
3. Rethman MP, Beltrán-Aguilar ED, Billings RJ, Hujoel PP, Katz BP,
Milgrom P, Sohn W, Stamm JW, Watson G, Wolff M, Wright JT, Zero
D, Aravamudhan K, Frantsve-Hawley J, Meyer DM; American Dental
Association Council on Scientific Affairs Expert Panel on Nonfluoride
Caries-Preventive Agents. Nonfluoride caries-preventive agents:
executive summary of evidence-based clinical recommendations. J Am
Dent Assoc. 2011; 142(9):1065-1071.
4. Schroeder H E. Formation and Inhibition of Dental Calculus. Hans
Huber, Berlin 1969; 145-172.
5. Löe H, Von der Fehr FR, Schiött CR. Inhibition of experimental caries
by plaque prevention. The effect of chlorhexidine mouthrinses Scand J
Dent Res. 1972;80(1):1-9
6. Corbet EF, Tam JO, Zee KY, Wong MC, Lo EC, Mombelli AW.
Therapeutic effects of supervised Chlorhexidine mouthrinses on
untreated gingivitis. Oral Dis. 1997; 3:9–18.
7. Grenier D, Effect of chlorhexidine on the adherence properties of
Porphyromonas gingivalis, J Clin Periodontol. 1996 Feb; 23(2):140-2.
8. Vianna ME, Gomes BP, Berber VB, Zaia AA, Ferraz CC, de Souza-
Filho FJ. In vitro evaluation of the antimicrobial activity of
chlorhexidine and sodium hypochlorite. Oral Surg, Oral Med, Oral
Pathol, Oral Radiol Endod. Jan 97(1), 79–84.
9. Bonesvoll P,Gjermo P. A comparison between chlorhexidine and some
quaternary ammonium compounds with regard to retention,salivary
concentration and plaque inhibiting effect in human mouth after mouth
rinses. Arch Oral biol 1978, 23; 289-294.
10. Hoffmann, T., Bruhn, G., Richter, S., Netuschil,L. & Brecx, M. clinical
controlledstudy on plaque and gingivitis reduction under long term use
of low dose chlorhexidine solutions in a population exhibiting good
oral hygiene. Clin Oral Investig 2001, 5: 89–95.
11. Van de weijden GA, Timmerman MF, Novtny GA, Rosema N, Verkerk
A, Three different rinsing times and inhibition of plaque accumulation
with chlorhexidine, J Clin Periodontol 2005, 32(1):89-92.
12. Regolati, B.; Schmid, R.; and Muhlemann, H.R.: Combination of
Chlorhexidine and Fluoride in Caries Prevention. An Animal
Experiment, Helv Odont Acta 1974,18: 12-16.
13. Lorenz K, BruhnG, Heumann C, NetuschilL, Brecx M, Hoffmann;
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, Aug 2006; 33(8):561-7
14. Barkvoll, Marinho, Home use oral hygiene products: mouthrinses, J
Clin Periodontol, Oct 2008,48 (1):42-53,
15. Addy M,Moran JM, Clinical indications for the use of chemical
adjuncts to plaque control, Periodontol 2000, 1997 Oct;15:52-54.
16. Dolles, Gjermo, The effects of a chlorhexidine toothpaste on the
development of plaque,gingivitis and tooth staining, J Clin
Periodontol, January 1993, 20,59-62.
17. Kalaga A, Addy M, Hunter B: The use of a 0.2% chlorhexidine spray
as an adjunct to oral hygiene and gingival health in physically and
mentally handicapped adults. J Periodontol 1989, 60: 381–385.
18. Matthijs S, Adriaens P A, Chlorhexidine varnishes: a review, J
Periodontol, 2002, 29:1-8.
19. Ainamo J, Etemadzadeh H, Prevention of plaque growth with chewing
gum containing chlorhexidine acetate, J Clin Periodontol
20. Zimmer, S., Kolbe, C., Kaiser, G., Krage, T., Ommerborn, M. &
Barthel, C. Clinical efficiency of flossing versus use of antimicrobial
rinses. J Periodontal 2006 Aug; 77(8):1380-5.
21. De Araujo Nobre M, Cintra N, Malo P, Peri implant maintainance of
immediate function implants:a pilot study comparing hyaluronic acid
and chlorhexidine, Int J Dent Hyg. 2007 May;5(2):87-94.
22. Roncati M, Polizzi E, Cingano L, Lucchese A, An oral health aid for
disabled patients, Dent Cadmos 2013; 81(7):447-452
23. Quirynen M, Mongradi, van steenberghe D, The effect of a one stage
full mouth disinfectionon oral malodour and microbial colonization of
tongue in periodontitis, J Periodontol 1998,69(3): 374-82.
24. Greenstein G, Berman C, Jaffin R, Chlorhexidine. An adjunct to
periodontal therapy. J Periodontol 1986; 57 (6): 370-6.
25. Sridhar V, Wali GG, Shyla HN, Evaluation of the Perioperative Use of
0.2% Chlorhexidine Gluconate for the Prevention of Alveolar Osteitis
After the Extraction of Impacted Mandibular Third Molars: A Clinical
Study. J Maxillofac Oral Surg. 2011 Jun;10(2):101-11
26. Angelo J. Mariotti, Chlorhexidine-Induced Changes to Human
Gingival Fibroblast Collagen and Non-Collagen Protein Production, J
Periodontol, Dec 1999; 70(12):1443-1448
27. Winkel EG, Roldán S, Van Winkelhoff AJ, Herrera D, Sanz M,
Clinical effects of a new mouthrinse containing chlorhexidine,
cetylpyridinium chloride and zinc-lactate on oral halitosis. A dual-
center, double-blind placebo-controlled study, J Clin Periodontol. 2003
28. van Steenberghe D, Avontroodt P, Peeters W, Pauwels M, Coucke
W, Lijnen A, Quirynen M, Effect of different mouthrinses on morning
breath, J Periodontol, 2001; 72(9):1183-1191.
29. Ferguson JW, Hatton JF, Gillespie MJ, Effectiveness of intracanal
irrigants and medications against the yeast Candida albicans. J Endod
2002; 28(2): 68–71.
30. Takahashi Y, Turkun M, Ertugul,Ates M,Brugger S, Long term
antibacterial effects and physical properties of chlorhexidine containing
glass ionomer cement, J Esthet Restor Dent, 2008, 20(11):29-45.
31. Soskolne WA, Heasma PA, Stabholz A, Smart GJ, Palmer M, Flashner
M, Newman HN, Sustained local drug delivery of chlorhexidine in the
treatment of periodontitis. J Periodontol. 1997 Jan;68(1):32-8
32. Jan Lindhe. Clinical Periodontology and Implant Dentistry, Fifth
edition. Blackwell Munksgard Publications, 2007.
33. Flotra L, Gjermo P, Rolla G, Waerhaug J: Side effects of chlorhexidine
mouthwashes. Scand J Dent Res, 1971; 79: 119–125.
34. EriksonH M, Nordbo H, Kantanen H, Ellingsen J E: Chemical plaque
control and extrinsic tooth discolouration. A review of possible
mechanisms. J Clin Periodontol, 1985; 12: 345–350.
35. Kolahi J, Soolari A, Rinsing with chlorhexidine gluconate solution
after brushing and flossing teeth: a systematic review of effectiveness.
Quintessence Int. 2006 Sep;37(8):605-12
36. Gordon J M, Lamster I B, Sieger M C. Efficacy of Listerine antiseptic
in inhibiting the development of plaque and gingivitis. J Clin
Periodontol 1985; 12: 697-704.
37. Harper P R, Milsom S, Wade W, Addy M, Moran J, Newcombe R G.
An approach to efficacy screening of mouthrinses: studies on a group
of French products (II) Inhibition of salivary bacteria and plaque in
vivo. J Clin Periodontol 1995; 22: 723-727
38. Flemingson , Emmadi P, Ambalavanan N,Ramakrishnan T
Vijayalakshmi R, Effect of three commercial mouth rinses on cultured
human gingival fibroblast: an in vitro study, Indian J Dent Res 2008
Jan-Mar; 19(1) :29-35.
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... [37] A "gold standard" of antiplaque agents. [30] Effective against bacteria and yeasts by disrupting their inner cell membranes. [30,31] Plaque adhesion is prevented as the acidic groups of salivary glycoproteins are blocked by chlorhexidine. ...
... [30] Effective against bacteria and yeasts by disrupting their inner cell membranes. [30,31] Plaque adhesion is prevented as the acidic groups of salivary glycoproteins are blocked by chlorhexidine. ...
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Numerous epithelial cells and sometimes leukocytes release AMPs as their first line of defense. AMPs encompass cationic histatins, defensins, and cathelicidin to encounter oral pathogens with minimal resistance. However, their concentrations are significantly below the effective levels and AMPs are unstable under physiological conditions due to proteolysis, acid hydrolysis, and salt effects. In parallel to a search for more effective AMPs from natural sources, considerable efforts have focused on synthetic stable and low-cytotoxicy AMPs with significant activities against microorganisms. Using natural AMP templates, various attempts have been used to synthesize sAMPs with different charges, hydrophobicity, chain length, amino acid sequence, and amphipathicity. Thus far, sAMPs have been designed to target Streptococcus mutans and other common oral pathogens. Apart from sAMPs with antifungal activities against Candida albicans, future endeavors should focus on sAMPs with capabilities to promote remineralization and antibacterial adhesion. Delivery systems using nanomaterials and biomolecules are promising to stabilize, reduce cytotoxicity, and improve the antimicrobial activities of AMPs against oral pathogens. Nanostructured AMPs will soon become a viable alternative to antibiotics due to their antimicrobial mechanisms, broad-spectrum antimicrobial activity, low drug residue, and ease of synthesis and modification.
... In a past investigation, Hellstein et al. (1993) explained that the affected Candida could exhibit abnormal colonies and cell morphology under a suppression phase. The presence of uncommon colonies and cells, especially in pathogenic oral bacteria, will increase the frequency of phenotypic switching by cells that cause the survival of Candida cells in a stressed growth environment (Fathilah et al., 2012;Balagopal & Arjunkumar, 2013). On the other hand, the results of this study show that none of the herbal mouth rinses produced antifungal effects on the Candida species. ...
... In summary, mouth rinse B, which contained CPC, was the most effective in all tests, except TKA, compared to mouth rinses A (CHX), C (CHX+CPC), and D (HEX). In most situations, CHX remains the gold standard antiplaque agent, and this active compound can be found in most commercialized mouth rinses worldwide (Balagopal & Arjunkumar, 2013). The long-term use of CHX-mouth rinses can cause teeth and tongue discoloration, parageusia, irritation, and hypersensitivity reactions to the oral mucosa (James et al., 2017). ...
Mouth rinses which function as breath fresheners, medicaments, and antiseptics can also deliver oral therapeutic agents. This study evaluated and compared the antifungal effects of synthetic and herbal mouth rinses on oral C. albicans and C. glabrata via disk diffusion, minimal inhibition concentration (MIC), minimum fungicidal concentration (MFC), time-kill assay, and growth profile tests. The four chemical mouth rinses, namely Brand O (A), Brand M (B), Brand H (C), and Brand B (D) used in the study showed positive antifungal activity in these two species. The average diameter of the inhibition zones obtained from the disk diffusion test was higher in mouth rinse B (C. albicans = 12.0 ± 0.9 mm, C. glabrata = 13.5 ± 0.8 mm) compared to those in C, A and D. Both Candida species exhibited similar MIC and MFC values, ranging from 1.63 ± 0.5 to 18.75 ± 0.0 µg/mL and 6.51 ± 2.01 to 50.00 ± 9.36 µg/mL, respectively. These synthetic mouth rinses had efficient killing activity eliminating 50% of the growing population of both Candida spp. following 15 seconds exposure time. Analyses of the growth profile curves showed that mouth rinses B and A resulted in rapid growth depletion of both Candida spp. Meanwhile, three herbal mouth rinses, namely Brand S (E), Brand C (F), and Brand P (G), were less effective against C. albicans and C. glabrata. Mouth rinses B and A contained cetylpyridinium chloride and chlorhexidine, respectively, and could be an effective alternative for controlling and preventing oral candidiasis.
... This may suggest that the dents and deformations caused by chlorhexidine only require the molecule to sit within the head groups. This may also explain why chlorhexidine works extremely quickly and is therefore an effective topical antiseptic, as it is not required to enter the membrane in order to have bacteriostatic and bactericidal effects 126 . However, we are limited by the timescales of MD and the particular force fields used. ...
Bacterial envelopes are a frontier that must be faced by all products that come into contact with them, including antibiotics, antiseptics and host defences. Many antimicrobials exploit features of the bacterial envelope in order to inhibit bacterial growth or cause cell death whilst the immune system recognises bacterial cell envelope patterns in order to mount an appropriate response. Given this, and the ever-growing concerns around antimicrobial resistance, it is vital that the mechanisms involved are well understood. This work used atomistic and coarse-grained molecular dynamics simulations to better understand the relationship between bacterial membranes and antimicrobials. The first chapter explored many of the aspects of the mode of action of membrane penetrating antibiotic, daptomycin. This investigated the relationship between daptomycin and calcium ions in addition to its dependence on phosphatidylglycerol. The second chapter of this work aimed to understand the mode of action of the membrane active antiseptic, chlorhexidine, on the Staphylococcus aureus membrane. The third chapter aimed to compare the differences of simulating chlorhexidine with the S. aureus membrane using different force fields. The final chapter focused on coarse- grain simulations of thrombin-derived C-terminal peptides (TCPs) with bacterial envelope products. This work aimed to support experimental work that had showed the co-aggregation of TCPs in the presence of bacterial envelope products as a mechanism to avoid host immune overreaction. <br/
... [2] Chlorhexidine (control) used in this study, is a proven chemical antimicrobial agent which shows bactericidal action by altering the integrity of the bacterial cell membrane thereby leading to coagulation and precipitation of the cytoplasm. [11] Also, Hugo et al in his ...
... Currently, CHX is considered the gold standard of antiseptics [16][17][18]; it possesses wide disinfection applicability to skin, wounds, and mucous membranes, and of no less important when treating urologic, gynecologic, and otorhinolaryngologic infections [19][20][21]. In dentistry, it has been broadly used to control dental plaque and gingivitis [17] and to prevent/ treat dental caries [21][22][23][24]. ...
Objectives This work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures. Methods CHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels’ biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e., leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey’s test (α = 0.05). Results CHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %. Significance The addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics.
... The antibacterial test of mouthwash achieved a noticeable positive result, %0.12 Bio fresh mouthwash produced largest zone of inhibition against Streptococcus mutans about (16 mm) then 1% coconut larger inhibition zone about (13 mm) then 0.8% about (6 mm) then 0.4% for (3 mm) [22][23][24]. ...
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Objectives: To analysis the benefit effect of coconut as natural mouthwash. Methods: This study depended on using of coconut as a main constituent in making a natural mouthwash solution. It examined some physical, chemical, biological and antibacterial properties of this mouthwash by surface tension test, pH measurement and antibacterial property of mouthwash as reduction of Streptococcus mutans count. Results: The results for 1% coconut mouthwash showed: surface tension (42.35 dyne/cm) and pH measurements (9.6), which was the highest results, while the antibacterial inhibition zone diameter for 1% coconut mouthwash was (13 mm) which the 2nd highest result. Conclusions: Coconut mouthwash plays an antibacterial effect with prevention demineralization of tooth enamel surface.
... The gold standard aiming at oral bacteria in the clinical treatment is the use of antibacterial agent chlorhexidine (Balagopal and Arjunkumar, 2013). Recent advances about the delivery of chlorhexidine in different carrier systems can achieve a slow release or controlled release of chlorhexidine for prolonging the releasing time and reducing drugs usage. ...
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The balance or dysbiosis of the microbial community is a major factor in maintaining human health or causing disease. The unique microenvironment of the oral cavity provides optimal conditions for colonization and proliferation of microbiota, regulated through complex biological signaling systems and interactions with the host. Once the oral microbiota is out of balance, microorganisms produce virulence factors and metabolites, which will cause dental caries, periodontal disease, etc. Microbial metabolism and host immune response change the local microenvironment in turn and further promote the excessive proliferation of dominant microbes in dysbiosis. As the product of interdisciplinary development of materials science, stomatology, and biomedical engineering, oral biomaterials are playing an increasingly important role in regulating the balance of the oral microbiome and treating oral diseases. In this perspective, we discuss the mechanisms underlying the pathogenesis of oral microbiota dysbiosis and introduce emerging materials focusing on oral microbiota dysbiosis in recent years, including inorganic materials, organic materials, and some biomolecules. In addition, the limitations of the current study and possible research trends are also summarized. It is hoped that this review can provide reference and enlightenment for subsequent research on effective treatment strategies for diseases related to oral microbiota dysbiosis.
Statement of problem Given the wide use of cobalt-chromium (Co-Cr) alloys, especially for removable partial dentures, and the importance of chemical solutions to complement the cleaning of dental prostheses, safe disinfection products should be identified for the regular decontamination of Co-Cr dental prostheses. Purpose The purpose of this systematic review of in vitro studies was to determine the effects on the properties of Co-Cr dental alloys of the various chemical agents used to clean dental prostheses. Material and methods In vitro studies were included based on a literature search conducted in March 2022 in the Medline/PubMed, SCOPUS, Web of Science, Virtual Health Library, and Embase databases. Independent reviewers performed the search, selection, extraction, and analysis of the data. The review was performed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The quality of the included articles was evaluated by using parameters adapted from the Consolidated Standards of Reporting Trials (CONSORT) guidelines, and the risk of bias analysis was performed based on previous studies. Results Among the 15 included studies, the chemical agents evaluated were alkaline peroxides and hypochlorites, mouthwashes containing cetylpyridinium chloride and chlorhexidine, diluted acids, and enzymes. Some peroxides produced increased ion release, surface roughness, and mass loss of the alloys. The hypochlorites were responsible for the greatest surface corrosion, yielding dark stains, rough regions, and depressions. Acetic and peracetic acids and mouthwashes containing chlorhexidine and cetylpyridinium did not produce significant changes in Co-Cr alloys. Most studies presented moderate risk of bias. Conclusions According to the included studies, mouth rinses containing cetylpyridinium chloride or chlorhexidine and solutions with acetic and peracetic acid could be safely used to chemically sanitize Co-Cr prostheses. Alkaline peroxides should be used with caution, and alkaline hypochlorite solutions should be avoided.
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Dental calculus in Detail
Background Plaque biofilm that adheres to tooth surfaces and gingiva is the main aetiology of periodontitis. Chlorhexidine (CHX) is considered as a gold standard anti-plaque and anti-gingivitis agent but it has side effects such as permanent staining of teeth and dysgeusia. Tea tree oil (TTO) is an essential oil extracted from the leaves of Melaleuca alternifolia. Many studies have reported that TTO exerts strong antibacterial, antifungal, antiviral and anti-inflammatory activities. Primary study objective The review aims to answer the question of whether TTO (intervention) is a viable alternative to CHX (comparator) for the management of gingival and periodontal disease (outcomes) in adolescents and adults (population). Methods/design The following search terms were used in PubMed, Scopus, Proquest, Web of Science, EBSCO (dentistry and open access), Cochrane database, and to search for relevant articles: patients with periodontal disease; OR periodontitis; OR gingivitis; OR gingival inflammation; AND essential oil; OR tea tree oil; OR Melaleuca alternifolia; AND chlorhexidine; AND reduction in gingival index; OR reduction in plaque index; OR reduction in bleeding from gums. The initial check for the title and abstract screening followed by removal of duplicates in Mendeley Reference Manager (version 1.19.4) based on the inclusion and exclusion criteria were performed. Primary outcome measures Parameters such as plaque index (PI), plaque surface score, gingival index (GI), bleeding index or bleeding as measured by % of sites with bleeding on probing (BOP) or bleeding scores, papillary bleeding index (PBI), were the primary outcomes considered. Results TTO is found to be superior to CHX in reducing signs of gingival inflammation; however, CHX is superior to TTO in inhibiting plaque formation, probably due to its increased substantivity. Conclusion TTO may be used as an alternative to CHX for reduction of gingival inflammation in conjunction with efficient plaque control measures.
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Aim: To examine the effect of three commercial mouth rinses (Hexidine 0.2%, Listerine Cool Mint, Betadine 1%) upon cultured human gingival fibroblast proliferation. Materials and Methods: Human gingival fibroblasts were cultured and incubated in Dulbecco′s Minimum Eagle′s Medium containing Chlorhexidine, Listerine, Povidone-Iodine at varying concentrations (1%, 2%, 5%, 10%, 20% and 100% of the given solution) at 37°C for 1, 5 and 15 min. Control cells received an equal volume of Dulbecco′s Minimum Eagle′s Medium without adding mouth rinses, for similar duration of exposure at 37°C. Following incubation the media were removed, cells were washed twice with medium, supplemented with 10% Fetal Bovine Serum, and fibroblasts in the test and control group were allowed to recover in the same media for 24 h. Results: In all the three groups, the proliferation inhibition was dependent on the concentration of solublized mouth rinses in the cell culture but independent of the duration of exposure to all three mouth rinses. The results showed that all three solutions were toxic to cultured human gingival fibroblasts, Chlorhexidine being the most cytotoxic. It was seen that at dilute concentrations (1% and 2% of given solutions) Listerine was more cytotoxic than Chlorhexidine and Povidone-Iodine. Conclusion: These results suggest that Chlorhexidine, Listerine and Povidone-Iodine are capable of inducing a dose-dependent reduction in cellular proliferation of fibroblasts. The results presented are interesting, but to know the clinical significance, further studies are needed.
Background. In this article, the authors present evidence-based clinical recommendations regarding the use of nonfluoride caries-preventive agents. The recommendations were developed by an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs. The panel addressed several questions regarding the efficacy of nonfluoride agents in reducing the incidence of caries and arresting or reversing the progression of caries. Types of Studies Reviewed. A panel of experts convened by the ADA Council on Scientific Affairs, in collaboration with ADA Division of Science staff, conducted a MEDLINE search to identify all randomized and nonrandomized clinical studies regarding the use of nonfluoride caries-preventive agents. Results. The panel reviewed evidence from 50 randomized controlled trials and 15 nonrandomized studies to assess the efficacy of various nonfluoride caries-preventive agents. Clinical Implications. The panel concluded that certain nonfluoride agents may provide some benefit as adjunctive therapies in children and adults at higher risk of developing caries. These recommendations are presented as a resource for dentists to consider in the clinical decision-making process. As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences. (The full report can be accessed at "".)
The effects on dental plaque, caries, molar surface dissolution rate and fluoride content of daily topical applications of 0.016 M solutions of chlorhexidine acetate (ChlAc), chlorhexidine hydrofluoride (ChlHF), chlorhexidine hydrochloride (ChlHCl) and of sodium fluoride (NaF) were tested in factorial arrangement in a short term rat caries test performed on 6 groups of 12 Osborne Mendel rats fed the high sucrose diet 2000a during a 20 day experimental period. Plaque formation was strongly inhibited by the readily soluble chlorhexidine compounds but not by NaF. Fluoride did not affect the plaque inhibiting properties of chlorhexidine. Smooth surface caries was strongly depressed by ChlAc, ChlHF and NaF but not by ChlHCl. Fissure caries was inhibited by both NaF and ChlAc and their effects were additive. While ChlHCl was ineffective, ChlHF was highly cariostatic. Molar surface dissolution rate and fluoride uptake were significantly influenced by chlorhexidine.
abstract – The purpose of this study was to test the hypothesis that a frequent intake of sucrose does not produce caries if the teeth are regularly treated with an antibacterial agent. Twenty-four students with clean teeth and normal gingivae were assigned to one of the following three groups: (1) eight individuals ceased all active oral hygiene measures and rinsed 9 times daily with 50% sucrose, (2) eight students refrained from all active oral hygiene procedures, rinsed 9 times daily with sucrose and twice daily with 10 ml 0.2% chlorhexidine gluconate, (3) the third group consisted of two subgroups each comprising 4 students. One subgroup ceased all oral hygiene procedures and rinsed twice daily with 0.2% chlorhexidine gluconate. The other was instructed to practice meticulous tooth brushing twice daily. The experiment lasted for 22 days. The group who rinsed with sucrose showed heavy plaque accumulation, those who rinsed with sucrose + chlorhexidine showed a drastic reduction in the formation of plaque. In the subgroup rinsing with chlorhexidine only and in that performing good oral hygiene, plaque was non-existent. The gingival state essentially paralleled the plaque formation. The sucrose group showed a definite increase in Caries Index. No significant changes occurred in the group rinsing with sucrose + chlorhexidine, with chlorhexidine only, or in the group performing good oral hygiene. It is concluded that prevention of plaque formation inhibits the development of gingivitis and dental caries, even with frequent rinses of sucrose.
To clinically evaluate the perioperative use of 0.2% chlorhexidine gluconate for the prevention of alveolar osteitis, to assess the patient compliance to chlorhexidine and to prepare a comprehensive treatment plan to prevent alveolar osteitis after removal of an impacted third molar extraction. A prospective study was done on 50 patients with bilaterally impacted lower third molars which were indicated for extraction. Extraction of impacted mandibular third molar on one side was done without using any mouthrinse. While extracting the third molar on the other side, patients were instructed to use chlorhexidine 0.2% mouth rinse for 8 days, 1 day preceding and 7 days following the surgery. They were instructed to use chlorhexidine 0.2% (Rexidine) mouth rinse for 30 s twice a day (before breakfast and after dinner) with 15 ml of the rinse with 1:1 dilution with clean water. All the patients were evaluated for pain, presence or absence of clot and condition of the alveolar bone for the diagnosis of dry socket. Incidence of dry sockets was 8%, when patients did not use 0.2% chlorhexidine gluconate perioperatively which is statistically significant. It appeared that the incidence of dry socket can be reduced significantly by using 0.2% chlorhexidne gluconate mouth rinse perioperatively (twice daily, 1 day before and 7 days after surgical extraction.
In this article, the authors present evidence-based clinical recommendations regarding the use of nonfluoride caries preventive agents. The recommendations were developed by an expert panel convened by the American Dental Association (ADA)Council on Scientific Affairs. The panel addressed several questions regarding the efficacy of nonfluoride agents in reducing the incidence of caries and arresting or reversing the progression of caries. A panel of experts convened by the ADA Council on Scientific Affairs, in collaboration with ADA Division of Science staff, conducted a MEDLINE search to identify all randomized and nonrandomized clinical studies regarding the use of non fluoride caries-preventive agents. The panel reviewed evidence from 50 randomized controlled trials and 15 nonrandomized studies to assess the efficacy of various nonfluoride caries-preventive agents. The panel concluded that certain nonfluoride agents may provide some benefit as adjunctive therapies in children and adults at higher risk of developing caries. These recommendations are presented as a resource for dentists to consider in the clinical decision-making process. As part of the evidence based approach to care, these clinical recommendations should be integrated with the practitioner’s professional judgment and the patient’s needs and preferences.
The oral retention of chlorhexidine, cetylpyridinium chloride and hexadecyltrimethylammonium bromide (a component of cetrimide) was measured by means of 14C-labelled compounds in 7 subjects after 10-ml 2.2 mM mouth rinses for 1 min. The oral retention of chlorhexidine was 32 ± 6 per cent, of cetylpyridinium chloride 65 ± 5 per cent and of hexadecyltrimethylammonium bromide 70 ± 7 per cent of the administered dose. The salivary concentration was measured after similar mouth rinses in 3 subjects and calculated according to the 14C-activity of saliva samples from 0.5 to 24 h after the rinsing. Although the concentrations of the quaternary ammonium compounds were usually higher than those of chlorhexidine shortly after rinsing, their concentrations were significantly lower (p < 0.001) than those of chlorhexidine from 4 h and onwards. The plaque-inhibiting effect was assessed in subjects who rinsed with 2.2 mM test solutions twice daily for 3 days, using sucrose rinses to provoke plaque formation. The plaque-inhibiting effect of the quaternary ammonium compounds was also tested when used in a mouth rinse four times daily. A moderate degree of plaque inhibition was obtained when the quaternary ammonium compounds were used twice daily. When the frequency was increased to four times daily, the plaque-inhibiting effect of the quaternary ammonium compounds seemed to approach that of chlorhexidine.
The extent and severity of periodontal attachment loss are described for a random sample of 690 dentate community-dwelling adults, aged 65 or over, residing in five counties in North Carolina. In addition, risk indicators for serious levels of loss of attachment and pocket depth in this population are presented. Pocket depths and recession were measured on all teeth by trained examines during household visits. Blacks had an average of 78% of their sites with attachment loss and the average level of loss in those sites was approximately 4 mm, as compared to 65% and 3.1 min for whites. Because the extent and severity scores in this population were much higher than in younger groups, a serious condition in this group was defined as having 4+ sites of loss of attachment of 5+ mm with one or more of those sites having a pocket of 4+ mm. Bivariate analyses identified a large number of explanatory variables that were associated with increased likelihood of having the more serious periodontal condition. The logistic regression model for blacks includes the following important explanatory variables and associated odds ratios: use to tobacco (2.9), colony counts of B. gingivalis greater than 2% (2.4) and B. intermedius greater than 2% (1.9), last visit to the dentist greater than 3 years (2.3), and gums bleeding in the last 2 weeks (3.9). The model for whites indicated that tobacco use (6.2), presence of B. gingivalis (2.4) and the combined variable of having not been to the dentist in the last 3 years and having a high BANA score (16.8) were important explanatory variables.(ABSTRACT TRUNCATED AT 250 WORDS)