Relationship of periodontal bacteria and <i>Porphyromonas gingivalis fimA</i> variations with phenytoin‐induced gingival overgrowth

Akiyama, Shuzo; Amano, Atsuo; Kato, Takahiro; Takada, Yasuhiro; Kimura, K. R.; Morisaki, Ichijiro

doi:10.1111/j.1601-0825.2005.01157.x

Cited by 15 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since plaque-induced gingival inflammation exacerbates the manifestations of PHT-induced GO [33], we exposed macrophage cultures to purified LPS from the periodontal pathogen, A. actinomycetemcomitans (Aa) and examined protein levels of MMPs, TIMPs and proinflammatory cytokines in conditioned media. Aa can be isolated from plaque samples of patients with GO [34] while Aa LPS, a TLR4 agonist, strongly induces MMP and pro-inflammatory cytokine expression [28-30,35]. …”

Section: Discussionmentioning

confidence: 99%

Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

et al. 2010

View full text Add to dashboard Cite

BackgroundPhenytoin (PHT) has been reported to induce gingival (gum) overgrowth (GO) in approximately 50% of patients taking this medication. While most studies have focused on the effects of PHT on the fibroblast in the pathophysiology underlying GO, few studies have investigated the potential regulatory role of macrophages in extracellular matrix (ECM) turnover and secretion of proinflammatory mediators. The aim of this study was to evaluate the effects of PHT and its metabolite, 5-(p-hydroxyphenyl-), 5-phenylhydantoin (HPPH) on LPS-elicited MMP, TIMP, TNF-α and IL-6 levels in macrophages.MethodsHuman primary monocyte-derived macrophages (n = 6 independent donors) were pretreated with 15-50 μg/mL PHT-Na+ or 15-50 μg/mL HPPH for 1 hour. Cells were then challenged with 100 ng/ml purified LPS from the periodontal pathogen, Aggregatibacter actinomycetemcomitans. Supernatants were collected after 24 hours and levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1, TIMP-2, TIMP-3, TIMP-4, TNF-α and IL-6 determined by multiplex analysis or enzyme-linked immunoadsorbent assay.ResultsA dose-dependent inhibition of MMP-1, MMP-3, MMP-9, TIMP-1 but not MMP-2 was noted in culture supernatants pretreated with PHT or HPPH prior to LPS challenge. MMP-12, TIMP-2, TIMP-3 and TIMP-2 were not detected in culture supernatants. High concentrations of PHT but not HPPH, blunted LPS-induced TNF-α production although neither significantly affected IL-6 levels.ConclusionThe ability of macrophages to mediate turnover of ECM via the production of metalloproteinases is compromised not only by PHT, but its metabolite, HPPH in a dose-dependent fashion. Further, the preferential dysregulation of macrophage-derived TNF-α but not IL-6 in response to bacterial challenge may provide an inflammatory environment facilitating collagen accumulation without the counteracting production of MMPs.

show abstract

Section: Discussionmentioning

confidence: 99%

Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Evidence suggests a role of genetic predisposition, intracellular calcium metabolism exchange, molecular mechanisms [cytokines such as epidermal growth factor (EGF), platelet‐derived growth factor‐P], inactivation of collagenase and inflammation induced by bacterial plaque 5 . Also, Porphyromonas gingivalis type II fimA and Treponema denticola were each found to have a significant relationship with the development and deterioration of phenytoin‐influenced gingival overgrowth 17 . Other aetiological hypothesis includes immunoglobulin A deficiency in serum and saliva leading to local immune reactions 18 , decreased serum folate levels causing deterioration of the gingival sulcular epithelium 19 and low calcium ions in gingival fibroblasts 20 .…”

Section: Discussionmentioning

confidence: 99%

“…1a). There was lobulated gingival overgrowth in the edentulous ridge and around the teeth present [18,17,13,27 and 28] in the upper arch ( Fig. 1b).…”

Section: Case Reportmentioning

confidence: 99%

Gingival overgrowth in partially edentulous ridges in an elderly female patient with epilepsy: a case report

Dhingra¹,

Prakash

2012

Gerodontology

View full text Add to dashboard Cite

Gingival overgrowth in partially edentulous ridges in an elderly female patient with epilepsy: a case report Background: Drug-influenced gingival overgrowth is an unaesthetic overgrowth of gingiva principally associated with intake of drugs like phenytoin, cyclosporin A and nifedipine. Its occurrence in both dentate and edentulous regions of oral cavity is poorly understood. Objectives: This report highlights clinical and histological description, aetiology and management of gingival overgrowth in a partially edentulous (non-denture wearer) 60-year-old female patient with epilepsy on phenytoin and phenobarbital drugs from past 7 years. Materials and methods: Patient's intraoral examination revealed lobulated and fibrotic consistency gingival overgrowth around teeth and on partially edentulous ridges of upper and lower arches along with generalised tooth mobility. Under medical consultation, full mouth extraction, surgical excision of overgrowth followed by complete denture rehabilitation and replacement of combination drugs with sodium valproate were accomplished. Results: Histologically, the lesion showed fibro-epithelial hyperplasia. Clinical results after 6 months demonstrated almost complete resolution of gingival overgrowth. Conclusion:The findings of present case suggest that gingival overgrowth can occur even in partially edentulous ridges (not exposed to denture wear) that could be due to persistence of gingival overgrowth, which may not resolve completely following tooth extraction or occurs because of incorporation of specific subpopulation of gingival fibroblasts in alveolar ridge mucosa.

show abstract

“…Takada et al [71] found that Prevotella intermedia (Pi) prevalence is higher in patients with PGO than in patients taking the medication but who did not develop that injury, and also those who did not use phenytoin. Akiyama et al [72] also examined subgingival bacterial profiles in subjects taking phenytoin who exhibited, or not, PGO. Quantitative analysis performed before and after periodontal treatment, revealed two bacterial species significantly associated with PGO, Treponema denticola (Td) and Porphyromonas gingivalis (Pg).…”

Section: Bacterial Biofilm and Pgo Developmentmentioning

confidence: 99%

Phenytoin-Induced Gingival Overgrowth: A Review of the Molecular, Immune, and Inflammatory Features

et al. 2011

View full text Add to dashboard Cite

Gingival overgrowth (GO) is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressant, and calcium channel blockers. GO is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components, with varying degrees of inflammation. One of the main drugs associated with GO is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. Nevertheless, the pathogenesis of such drug-induced GO remains fulfilled by some contradictory findings. This paper aims to present the most relevant studies regarding the molecular, immune, and inflammatory aspects of phenytoin-induced gingival overgrowth.

show abstract

Relationship of periodontal bacteria and Porphyromonas gingivalis fimA variations with phenytoin‐induced gingival overgrowth

Abstract: Type II Pg and Td were each found to have a significant relationship with the development and deterioration of GO.

Cited by 15 publications

References 27 publications

Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite,5-(p-hydroxyphenyl-), 5-phenylhydantoin

Gingival overgrowth in partially edentulous ridges in an elderly female patient with epilepsy: a case report

Phenytoin-Induced Gingival Overgrowth: A Review of the Molecular, Immune, and Inflammatory Features

Contact Info

Product

Resources

About