Effects of Combined Oral Treatments With Cyclosporine A and Nifedipine or Diltiazem on Drug‐Induced Gingival Overgrowth in Rats

Morisaki, Ichijiro; Fukui, Natsuko; Fujimori, Yasushi; Murakami, Jumpei; Daikoku, Hiroshi; Amano, Atsuo

doi:10.1902/jop.2000.71.3.438

Cited by 20 publications

(28 citation statements)

References 30 publications

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“…In fact, the fi ndings of previous investigations have shown that the administration of diltiazem in the doses used in the present study did not induce toxicity and that the treatment was well supported by the animals. 8,13,16,17 Macroscopically, the sucrose-rich diet induced dental biofi lm accumulations in all animals though none of them exhibited clinical characteristics of gingival overgrowth, which confi rms our previous fi ndings. 8 However, Morisaki et al 16 (2000) observed gingival overgrowth in rats after administration of diltiazem in doses greater than those used in the present study during a similar experimental period.…”

Section: Discussionsupporting

confidence: 86%

“…8,13,16,17 Macroscopically, the sucrose-rich diet induced dental biofi lm accumulations in all animals though none of them exhibited clinical characteristics of gingival overgrowth, which confi rms our previous fi ndings. 8 However, Morisaki et al 16 (2000) observed gingival overgrowth in rats after administration of diltiazem in doses greater than those used in the present study during a similar experimental period. Microscopically, there was only a mild infl ammation in the animals (Figure 1), which is particularly relevant because the diet followed by the animals was expected to cause gingivitis.…”

Section: Discussionsupporting

confidence: 86%

“…Correa et al 8 (2005) had similar results, although using lower doses of diltiazem. Another study 16 reported gingival overgrowth in rats after administration of diltiazem in doses > 1,000 mg/kg body weight for 40 days, which is much greater than the maximum dose used in our study (100 mg/kg). The rationale for choosing these doses of diltiazem was to simulate as close as possible the doses used in humans based on the fact that, in rats, 5 mg/kg correspond to the average daily intake of a hypertensive adult patient.…”

Section: Discussioncontrasting

confidence: 59%

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Influence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats

et al. 2009

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The aim of this study was to evaluate the infl uence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats. One hundred and twenty male Holtzman rats were randomly assigned to 10 groups (n = 12), being 2 control groups treated with saline and 8 test groups treated with diltiazem in daily doses of 5, 25, 50 and 100 mg/kg during 40 or 60 days. Afterwards, the mandibles were removed for macroscopic, histologic and histometric analyses of the buccal gingiva of the mandibular right fi rst molar. No macroscopic characteristic of gingival overgrowth was observed in any of the groups. The microscopic analysis showed characteristics of normality with infl ammatory cells only adjacent to the crevicular epithelium in all groups for both periods. The histometric analysis showed signifi cant differences only for the epithelial tissue area in the 40-day period (Kruskal-Wallis; P = 0.032). Comparing the periods, signifi cant differences regarding the connective and epithelial tissue areas were observed only in the group treated with a 25 mg/kg dose (Mann-Whitney; P = 0.004 and P = 0.007, respectively). Oral administration of diltiazem in combination with a sucrose-rich diet did not induce gingival alterations in rats.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 86%

Section: Discussioncontrasting

confidence: 59%

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Influence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats

et al. 2009

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“…Nos pacientes em uso de associação medicamentosa a presença de 70,8% de indivíduos com comprometimento gengival foi comparável àquela da maioria dos estudos relatados na literatura 16,19,27,34,37 . Nesses relatos, a associação dessas drogas provocou acometimento gengival geralmente mais intenso e 0,23 a 5,38 vezes mais freqüentes do que entre os que usaram somente a ciclosporina, sendo atribuída ao emprego de nifedipina em 15% a 44% dos usuários 25,38,39,40,41 . As diferenças observadas na freqüência de acometimento gengival podem ser imputadas à variação no sistema de avaliação.…”

Section: Discussionunclassified

Hipertrofia gengival em transplantados renais

Torrezan¹,

Sobrinho²,

Denardin³

et al. 2005

Rev. Assoc. Med. Bras.

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RESUMOOBJETIVO. Avaliar os fatores associados ao crescimento gengival excessivo em transplantados renais. MÉTODOS. A pesquisa foi realizada no Hospital Cajuru de Curitiba, no período de abril a outubro de 2002, com a participação de 60 transplantados renais, em uso diário de ciclosporina e com pelo menos um segmento dentário. O protocolo de ensaio foi observacional transversal. O exame odontológico dos indivíduos consistiu da avaliação dos segmentos dentários com verificação do grau de crescimento da gengiva e do índice de placa bacteriana. Todos os participantes preencheram questionário com dados relacionados ao transplante renal, realizaram coleta de material para controle do nível sérico de ciclosporina e foram avaliados quanto ao peso e altura. Na comparação dos resultados de amostras categóricas, utilizou-se o teste do Qui-quadrado e a correlação de classes de Spearman. O teste t foi aplicado na comparação das variáveis contínuas. RESULTADOS. Em pacientes tratados somente com ciclosporina, 47,2% não apresentavam alterações da gengiva, enquanto 52,8% cursaram com crescimento gengival, sendo 30,6% com grau ≥ 2. Nos pacientes tratados com ciclosporina e nifedipina, notou-se que 29,2% tinham gengiva normal e 70,8% apresentaram crescimento gengival, sendo que em 45,8% o comprometimento foi grau ≥ 2. Não foi observada diferença significativa dos resultados entre os gêneros masculino e feminino. Foi encontrada correlação positiva entre o índice de placa bacteriana e o volume gengival (r = 0,3295; p<0,01). CONCLUSÃO. Em transplantados renais, a hipertrofia gengival está associada ao uso de ciclosporina, isoladamente ou em concomitância com bloqueadores de cálcio, e apresenta uma correlação com o índice de placa bacteriana.UNITERMOS: Crescimento gengival. Ciclosporina. Nifedipina. INTRODUÇÃOA descoberta da ciclosporina como medicamento imunossupressor abriu um novo horizonte no controle da rejeição em transplantes renais 1,2 . O sucesso do seu uso sistemático trouxe como conseqüência natural a extensão da indicação terapêutica para algumas das manifestações de doenças auto-imunes 3,4,5 . Entre os efeitos adversos desta medicação, alguns autores observaram o aumento do volume gengival 6,7,8 . A molécula mãe, que parece ser a forma ativa, sofre transformação metabólica no fígado, resultando em 14 produtos metabólicos, dos quais 90% são excretados pelas fezes e 10% são eliminados pelos rins 9,10 . As alterações gengivais, induzidas por medicamentos, não são ocorrências infreqüentes e podem ser determinadas por drogas como fenitoína, nifedipina, verapamil e diltiazen. Em modelos animais, a prevalência da uvulopatia macroscópica é de 100% para qualquer uma das drogas, enquanto que nos humanos varia de 10% a 50% para a fenitoína, de 8% a 81% para a ciclosporina e de 0,5% a 83% para a nifedipina [11][12][13][14][15] , podendo atingir freqüência ainda maior com o uso combinado de ciclosporina e nifedipina 11,16,17 . Quanto ao limiar de concentração sérica, necessária para indução de hipertrofia gengival, alguns autores afir...

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“…Twenty-four 15-day-old, specifi c pathogen-free, male Fischer rats were purchased with their lactating dams from Charles River Japan and reared in a clean room at 25 ° C in the animal facility of Osaka University Graduate School of Dentistry. The animal experiment was performed basically according to the method of Morisaki et al [18,19] . Briefl y, the rat pups were divided into 4 groups (6 rats/group) for the experimental period of 41 days.…”

Section: Animals and Drug Administrationmentioning

confidence: 99%

Enhancement of Nifedipine-Induced Gingival Overgrowth by Concomitant Ketoconazole in Rats

Kato¹,

Amano²,

Kamisaki³

et al. 2005

Pharmacology

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Nifedipine (NIF), a calcium channel blocker, is well known to induce gingival overgrowth (GO) as an adverse effect, and ketoconazole (KTZ), an azole antifungal agent, has been implicated in various drug interactions. We here examined the effects of concomitant KTZ on NIF-induced GO in a rat model. Fifteen-day-old male Fischer rats were fed chow with NIF, KTZ, or both. After 41 days, gingival conditions were evaluated and the concentration of NIF in serum was measured. Rats fed with NIF alone had induced GO and suppressed growth, while those given KTZ alone did not. Compared to the administration of NIF alone, concomitant KTZ significantly increased the severity of GO and the concentration of NIF in serum. These results suggest that concomitant KTZ increases the serum concentration of NIF and enhances the severity of GO.

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Effects of Combined Oral Treatments With Cyclosporine A and Nifedipine or Diltiazem on Drug‐Induced Gingival Overgrowth in Rats

Abstract: These results suggest that gingival overgrowth is induced in rats as a side effect of CsA, nifedipine, or diltiazem, and the combined use of these drugs influences rat growth, blood drug levels, and the severity of gingival overgrowth.

Cited by 20 publications

References 30 publications

Influence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats

Influence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats

Hipertrofia gengival em transplantados renais

Enhancement of Nifedipine-Induced Gingival Overgrowth by Concomitant Ketoconazole in Rats

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