International Journal of Paediatric Dentistry 2006; 16: 174–180
Erosive effect of an antihistamine-containing syrup on primary enamel and its reduction by fluoride dentifrice C. C. COSTA1, I. C. S. ALMEIDA1 & L. C. COSTA FILHO1Santa Catarina Federal University, Florianópolis, Brazil and 2Pontificial Catholic University of Rio Grande do Sul, Porto Summary. Aim. This study evaluated the action of an antihistamine-containing syrup (Claritin D) on enamel that was
subsequently submitted or not to applications of fluoride dentifrice.
Methods. Two hundred sixty-four slices (n = 44 per subgroup) prepared from exfoliated primary molars were evaluated in hardness tests. Six subgroups were submitted to different treatments for 10 days. The controls underwent pH cycling with (positive control) or without (negative control) three daily immersions in fluoride dentifrice/distilled water slurry.
The test subgroups related to daytime use of the antihistamine syrup underwent pH cycling and two 5-min applications of Claritin D, coupled or not to the three daily immersions in the fluoride slurry. The subgroups related to nocturnal use of the syrup were submitted to the same procedures of daytime subgroups, respectively, but with one of the applications of Results. The median hardness values obtained after use of the syrup were significantly lower than the initial ones. Equivalent values for subgroups submitted to fluoride applications in addition to treatment with the syrup were significantly higher.
Conclusion. It was concluded that the antihistamine-containing syrup reduced the hardness of primary enamel and that, in this experiment, the use of fluoride dentifrice was able to diminish this erosive effect.
chronic diseases. Antihistamine-containing medicines Introduction
may be an example of a potentially erosive agent.
Dental caries is the most prevalent disease of the Besides the acid components found in such oral cavity and may affect individuals at any stage medications, other factors such as high frequency of of their lives. Nevertheless, tooth dissolution can ingestion (two or more times a day), bedtime con- also be caused by erosion, which is the mineral loss sumption, high viscosity, and the collateral effect of of dental tissue when its surface is exposed to acids a reduction in salivary flow may contribute to the or chelates, in a systematic manner and without Many recommendations have been made in order According to Linnett and Seow [2], the prevalence to minimize tooth damage caused by the regular use of dental erosion has increased especially among of liquid medications. Among these is the use of the children and adolescents. The aetiology has been medication at meal times in order to avoid ingestion related to the regular use of products with low between them [4]. Oral hygiene or mouth rinsing endogenous pH, high acidity, and absence or low with water or chewing sugar-free gum after taking concentrations of ions including those of calcium, the medication have also been recommended [3], as fluoride, and phosphate in their composition. Among have the addition of calcium, fluoride, or phosphate these products are medications that may be erosive to formulations [3] and the use of topical fluoride because they possess these characteristics, and which may be of a particular risk when used for treatment of Although the efficacy of fluoride in preventing dental caries is widely accepted, the same is notevident in relation to erosion, as the ability of Correspondence: C. C. Costa, Rua Gaspar Martins, 1882. Bairro treatments with fluoride to prevent the loss of dental Centro. Santa Maria, RS, Brazil. 97060-260. E-mail:[email protected] tissue through erosion is still questioned [1,5].
Effect of antihistamine syrup and dentifrice on primary enamel Unlike what occurs during the caries process, in citric acid, calcium, and phosphate, were also erosion the acid challenge is much stronger, and after determined. Tests demonstrated that the medication erosive mineral loss only a thin, partly demineral- did not contain fluoride or phosphate; the percentage ized and softened surface layer is left to provide of citric acid was 0·0147% and of calcium, a structure for remineralization. In addition, the stability of the calcium fluoride under erosive con-ditions is still unknown, but it may be speculated that this compound provides additional mineral tobe dissolved during an acid attack before the under- Samples were obtained from 88 exfoliated primary lying enamel is affected. Thus it may be hypothesized molars cut longitudinally, in a mesio-distal direc- that, in a similar way to its anticariogenic properties, tion, in slices 2 mm thick. The dental sections were fluoride may assist in strengthening hard tooth tissue invested in polyester resin (FiberGlass Ind. & Com.
against acids and re-harden an eroded enamel surface Ltda; Florianópolis, SC, Brazil) and, after polymer- ization, were smoothed (abrasive papers of sizes The aim of this in vitro research was to evaluate, 800, 1000, 1200, 1500 and 2000; 3M Ind. & Com.
through hardness tests, the action of Claritin D Ltda; St Paul, MN, USA) and polished (Arotec Ind.
syrup (Schering-Plough; São Paulo, SP, Brazil) on & Com. Ltda; São Paulo, SP, Brazil felt discs and the enamel of primary molars and the effect, if any, 1 and 0·3 µm oxide aluminium suspension, South of concomitant applications of fluoride dentifrice.
Bay Technology Inc.; San Clemente, CA, USA) ina water-cooled grinding machine (Panambra DP-10,Struers; São Paulo, SP, Brazil). After the polishing procedure, samples were viewed under an optical This experimental study evaluated, in vitro, the microscope (Aus Jena, model 444181, with a 40× hardness of 264 samples of primary enamel.
objective; Astro Optics Division, Montpelier, MD, USA) in order to check that surfaces were flat, pol- antihistamine-containing syrup, and fluoride denti- ished, and without irregularities that could interfere frice. The pH cycling simulated a low acid challenge in relation to feeding [7], and the antihistamine-containing syrup was applied to sound primary enamel in situations set up to represent its use during theday and at bedtime in order to investigate the action In order to make the indentations, the hardness of fluoride dentifrice on different usage patterns.
tester (Shimadzu, model HMV – 2000; Nakagyou,Kyoto, Japan) was calibrated with a Knoop tip andload of 50 g was applied for 5 s. The initial inden- tation was located in a standard position 1·5 mm Claritin D syrup (Schering-Plough) was selected below the cusp tip and 0·1 mm from the enamel for this study because it is frequently used for external surface. Three indentations, at the same chronic conditions and has the characteristics of low height, toward the dentin, spaced 100 µm from each endogenous pH (pH 3·84 ± 0·04) and high acidity other, were made and their average value was taken (30·69 mL ± 1·98 mL of NaOH 0·1 N solution to as equivalent to the hardness value of the specimen neutralize 100 mL of the diluted medication). Pre- liminary chemical analysis of the product was made Following the initial hardness test, 264 dental in triplicate using samples from three different sections with an enamel hardness value between batches. The pH was measured with a digital pH 272 and 440 Knoop hardness number (KHN) were meter (MP 220 – Mettler Toledo; São Paulo, SP, selected, as these were considered compatible with Brazil) and the titrable acidity by the method AOAC 22·058, which determines the quantity of NaOH0·1 N solution necessary for the product to reach neutral pH or pH above it (pH ≥ 7·0) [8].
Chemical parameters considered important in Sections were next allocated into control and Claritin D syrup, such as quantities of fluoride, experimental groups and into six subgroups. Two C. C. Costa, I. C. S. Almeida & L. C. Costa Filho Fig. 1. (a) Hardness tester with Knoop
tip. (b) Drawing of the dental slice: initial
position of the hardness tester tip and
dislocation direction. (c) Enlargement of
drawing b: from the external limit (in
contact with the resin) there is a space
of 100 µm among the indentations.
formed control groups (positive and negative) and Two subgroups belonging to the experimental group four were experimental groups representing daytime were submitted to pH cycling and to antihistamine medication, daytime medication + fluoride dentifrice, syrup application, representing daily and daytime nighttime medication, and nighttime medication + use for 10 days (E1) or daily and nighttime use for the same period of time (E3). The amount of syrup Cycles of demineralization and remineralization used for each sample was the equivalent of 0·25 mL were based on the pH cycling proposed by Ten Cate two times a day. In subgroup E1, the applications and Duijsters [7] and modified by Featherstone et al.
lasted for 5 min each and in subgroup E3, one of [10]. This cycling includes 10 cycles in which the them lasted for 5 min and the other for 8 h.
samples are immersed daily, at 37 °C, for 3 h in the To evaluate the topical effect of daily use of fluo- demineralizing solution followed by 21 h in the rem- ride dentifrice on the primary enamel that received antihistamine syrup application, two subgroups were Thus, each 1 mm2 of dental tissue was immersed included in the experimental group. Each specimen in 6·24 mL of demineralizing solution (acetate buffer from subgroup E2 had the same treatment as subgroup 75 mm containing 2·0 mm of Ca and P at pH 4·3) E1 added to the utilization of fluoride dentifrice/ and in 3·12 mL of remineralizing solution (Tris distilled water slurry (1 min immersion in fluoride buffer 0·1 m containing 1·5 mm Ca, 0·9 mm P, and dentifrice/distilled water slurry three times a day).
150 mm KCl at pH 7·0). Because this cycling The samples from subgroup E4 underwent the was carried out for 14 days and involved 10 cycles same procedures as subgroup E3 plus use of the of pH, after the fifth day the samples were stored in remineralizing solution for 48 h, after which both Strategies of treatment for each subgroup, over a solutions were changed for a new cycle of 5 days period of 24 h, are summarized below.
C1 (negative control subgroup): demineralizing The samples from the control group were sub- solution for 1 h + remineralizing solution for 4 h + mitted only to pH cycling (negative control – C1) or to pH cycling added to immersion in slurry of fluo- solution for 6 h + demineralizing solution for 1 h + ride dentifrice (Tandy, Kolynos-Brazil, silex-based gel with 1·1 mg /g F in NaF form) and distilled water C2 (positive control subgroup): demineralizing (proportion 1 : 3) that presented 0·948 mg /g of flu- solution for 1 h + fluoride dentifrice/distilled water oride and pH of 7·2 (positive control – C2). The slurry for 1 min + remineralizing solution for 4 h + specimens were immersed in the slurry of fluoride demineralizing solution for 1 h + fluoride dentifrice/ dentifrice and distilled water, 0·625 mL/mm2, for 1 min on three occasions, in order to simulate the solution for 6 h + demineralizing solution for 1 h + topical action exerted by the fluoride during tooth fluoride dentifrice/distilled water slurry for 1 min + Effect of antihistamine syrup and dentifrice on primary enamel E1 (experimental subgroup simulating daily and indentations were firstly located in carry out the daytime use of medication): demineralizing solution for 1 h + remineralizing solution for 2 h + applicationof medication for 5 min + remineralizing solution for 2 h + demineralizing solution for 1 h + remineralizingsolution for 6 h + demineralizing solution for 1 h The software sas system 8·02 for Windows (SAS + remineralizing solution for 2 h + application of Institute Inc. – Cary, NC, USA) was used for the medication for 5 min + remineralizing solution for 9 h.
statistical analysis, using analysis of variance with E2 (experimental subgroup simulating daily and mixed models. To analyse hardness before and after daytime use of medication and of fluoride denti- the specific treatments, two mixed models were made in which the dependent variable was initial dentifrice/distilled water slurry for 1 min + reminer- and final hardness, respectively, and the fixed effects alizing solution for 2 h + application of medication (explanatory variables) were subgroup and indenta- for 5 min + remineralizing solution for 2 h + tion number (which represent enamel depth), demineralizing solution for 1 h + fluoride dentifrice/ whereas the random effect was the sample number.
After the treatments, the initial hardness was used solution for 6 h + demineralizing solution for 1 h as a co-variable in the final hardness model to increase + remineralizing solution for 2 h + application of statistical power and to better adjust the model. A medication for 5 min + fluoride dentifrice/distilled third mixed model was made, keeping the same water slurry for 1 min + remineralizing solution for 9 h.
fixed and random effects, but considering the per- E3 (experimental subgroup simulating daily and centual reduction in hardness as the dependent nighttime use of medication): demineralizing solu- The covariance structure used was the variance com- application of medication for 5 min + remineralizing ponents, and the method to estimate the differences solution for 2 h + demineralizing solution for 1 h + among subgroups and indentations was the Tukey– Kramer with significance level of 1% (P < 0·01).
solution for 1 h + remineralizing solution for 2 h +application of medication for 8 h + remineralizing E4 (experimental subgroup simulating daily and Pre-treatment hardness values among the six sub- nighttime use of medication and of fluoride denti- groups did not show a statistically significant differ- ence (P = 0·3687). All mean values were greater dentifrice/distilled water slurry for 1 min + reminer- alizing solution for 2 h + application of medication for The mean hardness values obtained for the six 5 min + remineralizing solution for 2 h + demineraliz- subgroups after the different treatments were all sig- ing solution for 1 h + fluoride dentifrice/distilled nificantly lower than equivalent pretreatment values water slurry for 1 min + remineralizing solution (P < 0·001) (Table 1 and Fig. 2), demonstrating that for 6 h + demineralizing solution for 1 h + fluoride there had been loss of hardness in all subgroups.
dentifrice/distilled water slurry for 1 min + reminer- In subgroup C1 (pH cycling), there was a decrease alizing solution for 2 h + application of medication in hardness of 20·28% and the mean of post- for 8 h + remineralizing solution for 1 h.
treatment values was 266·16 KHN. In subgroup C2(pH cycling and fluoride application), the decreasein hardness was only 5·31% and the mean hardness after treatment was still compatible with sound Identifications marks on the samples were covered with adhesives and were mixed for blind estimations Subgroup E1 (pH cycling and daytime medication use) showed a decrease of 46·83% in enamel hard- The final hardness analysis was performed by the ness and mean hardness after treatment (179·29 same examiner in exactly the same way as the initial KHN) was considered representative of demineral- assessment, using the same instrument, number of ized human enamel. In subgroup E2 (same treatment indentations, load, and application time. The initial as E1 added to fluoride application), the decrease in C. C. Costa, I. C. S. Almeida & L. C. Costa Filho Table 1. Mean values in KHN and hardness variation after treatments in the six subgroups.
Equal superscripts indicated statistical equivalence (P > 0·36).
Different superscripts indicated statistical difference (P < 0·0001).
The values in parentheses indicated the confidence intervals of 95% of the means estimated by the three mixed models.
Among these properties are: low endogenous pH[12], high titrable acidity [12], presence of citricacid [13], absence of fluoride and phosphate, andminimal quantity of calcium in its composition [14].
It is common knowledge that the chemistry of enamel changes from its surface to interior and thiswas evident in the present study, because the inter-nal indentations had lower hardness values than didthe external ones. As the mixed model statisticincorporated the coverable indentation depth andthere was no interaction with the different treat-ments, showing that enamel reaction was uniformdespite its depth and suggesting that it was unlikely Fig. 2. Mean Knoop hardness values for the six subgroups before
to have acted as a confounder. Thus, investigations using surface tissue may be directly compared tothis research.
hardness was lower, at 14·59%, and the post-treatment Subgroup C1 had a substantial loss of mineral, indicating that the immersion of enamel in a rem- The subgroup E3 (pH cycling and nighttime med- ineralizing solution, with a composition similar to ication use) showed the greatest decrease in enamel human saliva, for 21 h daily, was not enough to hardness, at 89·14%, and the final hardness value prevent the demineralization caused by three acid was only 36·32 KHN. In subgroup E4 (same treat- attacks. These findings corroborated the study of ment as E3 added to fluoride application), the hard- Eisenburger et al. [15] in which artificial saliva was ness decrease was also high, 84·49%, and final not able to restore the superficial hardness or mor- hardness value was 51·75 KHN (Table 1 and Fig. 2).
phology of the eroded dental samples. The results Among the mean values for hardness obtained of subgroup C2 supported the findings of studies after the different treatments, statistically significant [16,17] in which the enamel specimens treated with differences (P < 0·001) were detected among the six dentifrice containing sodium fluoride showed an subgroups (Table 1). Values for subgroups submitted increase in hardness, indicating remineralization.
to fluoride application were significantly greater All subgroups where treatment utilized antihista- than were values for subgroups that did not have mine-containing syrup showed statistically signifi- cant decreases in hardness values when compared to control subgroups. This was irrespective of patternof treatment.
Considering subgroup E1, it can be suggested Discussion
that five daily acid challenges were able to cause Claritin D syrup (Schering-Plough) presents charac- considerable enamel demineralization. In subgroup teristics that may well provide erosive potential.
E3, it was demonstrated that prolonged exposure Effect of antihistamine syrup and dentifrice on primary enamel of primary enamel to an acid medication caused an frice is able to diminish erosion in vitro, it seems extremely aggressive demineralization that resulted likely to do the same in vivo. In addition, if more in a reduction of the final hardness mean almost concentrated fluoride agents could be used simulta- five times greater than did shorter exposure to the neously, even better protection of dental tissues same product. The increase in exposure time to acid would be assured and, possibly, erosion would be products that worsened the occurrence of erosion has also been described by Hunter et al. [18].
It was possible to conclude that the final hardness Results for the subgroups submitted to medication values for subgroups that received application of and fluoride applications (E2 and E4) showed that Claritin D syrup (E1 and E3) were significantly fluoride is capable of reducing the erosive effect of lower than values in the control subgroup (C1). This an acid product, because it provides enamel protec- difference was reduced by the fluoride dentifrice/ tion in relation to its hardness. Similar findings were distilled water slurry, because the subgroups submit- demonstrated in the studies with dentifrice [19], ted to topical fluoride treatment (C2, E2, and E4) varnish [4], gel, and fluoride solution [20], which presented final hardness values that were signifi- have led to the conclusion that different forms of cantly greater than those of homologue subgroups fluoridation are able to minimize enamel and dentin without fluoride treatment (C1, E1, and E3).
The results of subgroup E4 showed that the What this paper adds
presence of fluoride was not enough to prevent an • This paper adds information that an acid medication can accentuated demineralization because of prolonged reduce deciduous enamel hardness, especially when in acid challenge and that, perhaps, the application of contact with this tissue for a prolonged period of timeand without the presence of fluoride in the environment.
additional fluoride in solutions, gels, or varnishes,as suggested by some authors [20], may be Why this paper is important for paediatric dentists
employed in order to protect dental tissues in an • Paediatric dentists must be aware of the potential demineralization an acid medication can bring to deciduous enamel and also should have in mind that a Many researches have indicated that the action of fluoride toothpaste can attenuate this harmful effect.
topical fluoride in dental erosion prevention is ques-tionable [5,21] or that this ion only provides a pre-ventive effect when applied in high concentrations[4,20]. Results of this study are contrary to these References
findings, since the fluoride dentifrice/distilled waterslurry was able to reduce the erosive process.
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