DZZ Ausgabe 08/2004

The effect of amine fluoride/stannous fluoride, triclosan and acetylsalicylic acid on experimental gingivitis

This placebo-controlled double-blind study was aimed at determining the effects of mouthrinses containing amine fluoride/stannous fluoride (AmF/SnF2), triclosan and acetylsalicylic acid (ASA) on the levels of prostaglandin E2 (PGE2); leukotriene B4 (LTB4) and thromboxane B2 (TxB2) in gingival crevicular fluid (GCF) during experimental gingivitis and subsequent rinsing phase. 44 subjects participated in the study. To establish healthy gingival conditions, all subjects underwent a 3-week period of professional tooth cleaning and oral hygiene instruction. Plaque and gingivitis assessments, microbial sampling and gingival crevicular fluid assessment were performed at baseline. At the second examination healthy conditions were recorded. For the next 14 days, the subjects were asked to abstain from any form of oral hygiene (experimental gingivitis phase). The 3rd and 4th examinations were performed 7 and 14 days after the 2nd examination and was followed by random assignment of mouthrinses containing either AmF/SnF2, triclosan, ASA or placebo. These mouthrinses were used for 22 days with no additional oral hygiene measures (rinsing phase). During this period the 5th and 6th examinations were performed at 25 and 36 days after the 2nd examination. Immunological evaluation of the gingival crevicular fluid (GCF) was done by enzyme immunoassay with respect to PGE2, LTB4 and TxB2. Statistical analysis was based on the Kruskal-Wallis test and the Wilcoxon-Mann-Whitney test. The findings revealed no significant change in TxB2 levels during the experimental gingivitis phase for all subjects, while the PGE2 levels showed a significant increase between the 2nd and 4th examinations. Combined data from all subjects revealed significant reductions in PGE2 and LTB4 during the rinsing phase between the 4th and 5th examinations, while TxB2 levels were increased during the rinsing phase. However, no statistically significant inter-group differences were observed in reducing the GCF inflammatory mediators between the rinsing solutions after a 22 days rinsing period.
1 Introduction There is ample evidence that bacterial plaque plays a decisive role in the initiation and progression of periodontal disease [17]. The major goal of periodontal treatment is to eliminate supra- and subgingival plaque, and subsequently to prevent microbial recolonization of the subgingival area by plaque control measures. To achieve this therapeutic goal, various types of antiseptics have been introduced and evaluated. The efficacy of chlorhexidine in particular has been verified in numerous studies [6, 14]. However, its side effects preclude its long-term daily use [1, 2, 7], directing research towards the development of safe and effective chemical antiplaque agents. One such agent is an aminefluoride/stannous fluoride solution, with stannous fluoride showing an antimicrobial effect [33, 13] combined with the caries inhibitory effect of amine fluoride [19, 20]. The stability problems inherent in stannous fluoride have prevented its use in oral prophylaxis. The first stable mouthrinse containing both substances was produced by GABA International AG (Basle/Switzerland) under the trade name Meridol. The same AmF/SnF2 combination has also been stabilized in a toothpaste. This beneficial effect was demonstrated by long-term studies showing a reduction in clinical signs of inflammation as well as in pathogenic microorganisms [18, 37]. However, whether AmF/SnF2 also has an anti-inflammatory effect on the gingiva has not yet been elucidated. Triclosan is a phenol derivative [2,4,4’-trichloro-2’-hydroxy-diphenylether) which has been widely used as a supplementary personal hygiene product to prevent bacterial contamination. It has been included in mouthrinses and toothpastes. Clinical studies have confirmed that dentifrices containing triclosan plus a copolymer and sodium fluoride significantly retard the formation of plaque and plaque-associated gingivitis [35] and reduce the incidence of dental caries [21]. The number of anaerobic bacteria and of actinomycetes in plaque has been shown to be reduced after 21 days’ exposure to triclosan [11]. Waaler et al. [36] and Kjærheim et al. [12] demonstrated that topical application of triclosan to both intraoral and extraoral compartments reduced clinical signs of inflammation. Ramberg et al. [26] showed in an experimental gingivitis study that triclosan incorporated in a mouthrinse inhibited or retarded gingival inflammation which would otherwise have developed in the presence of plaque. Triclosan can penetrate skin and mucous membranes [3, 36] and has antiphlogistic traits. In an in vitro study based on cell culture experiments, Gaffar et al. [5] found that triclosan inhibited interleukin 1b-induced prostaglandin E2 production by human gingival fibroblasts in a concentration-dependent manner and at relatively low concentrations. These data suggest that, in addition to its antibacterial effect, triclosan can also inhibit formation of several important mediators of gingival inflammation in vitro. Systemic administration of non-steroidal anti-nflammatory drugs (NSAID) such as acetylsalicylic acid (ASA) can reduce the development and progression of periodontal diseases [24]. Flemmig et al. [4] assessed the effect of systemically administrated ASA combined with conventional periodontal therapy and suggested that the combination of therapies reduced bacterial plaque and inhibited destructive components of the immune response. As systemic administration of NSAID has not been established as a routine method for preventing and/or treating periodontal disease due to its side effects, topical application has been proposed. A significant reduction in gingival inflammation following by rinsing with 0.3% ASA over a 3–4 week period was reported by Reiff et al. [27].

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