Plasma and Gingival Crevicular Fluid Phenytoin Concentrations as Risk Factors for Gingival Overgrowth

Güncü, Güliz N.; Çağlayan, Feriha; Dinçel, Aysun; Bozkurt, Atilla; Saygı, Serap; Karabulut, Erdem

doi:10.1902/jop.2006.060103

Cited by 20 publications

(19 citation statements)

References 53 publications

(166 reference statements)

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“…And while PHT plasma levels of 10-20 μg/mL are necessary to effectively maintain effective seizure control [22-24], disturbances in plasma as well as gingival concentrations of PHT are likely associated with DIGO. Indeed, Güncü et al [36] compared PHT levels in plasma and gingival crevicular fluid (GCF), a serum exudate, from subjects who demonstrated gingival overgrowth (responders) vs. those who did not (non-responders). Although PHT was detected in all of the GCF and plasma samples, the mean concentration of PHT was significantly greater in GCF compared to plasma (294.99 ± 430.15 μg/mL vs. 16.09 ± 4.21 μg/mL, respectively).…”

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

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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.

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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

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“…Gingival hypertrophy is a major side effects associated with the administration of phenytoin. The mechanism by which phenytoin induces gingival hypertrophy is not well understood but we know that plasma phenytoin level and long-term use appear to be a risk factor for the appearance of this adverse effect [26]. In our patient, phenytoin was administered in a low dose (100 mg/day) and a short-term use of six months.…”

Section: Discussionmentioning

confidence: 93%

Phenytoin in the Treatment of Osmophobia in Migraine Patient: A Case Report

Silva‐Néto¹

2016

J Clin Case Rep

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“…Phenytoin is one of the most commonly prescribed medications to treat epilepsy and may also be used in cases of neuralgias and cardiac arrhythmias (18). It is estimated that about 30% to 50% of patients taking phenytoin develop significant gingival alterations (19).…”

Section: Discussionmentioning

confidence: 99%

Wound Healing Potential of Topical Amlodipine in Full Thickness Wound of Rabbit

Hemmati

Forushani

Asgari

2014

Jundishapur J Nat Pharm Prod

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Background: Wound healing is a complicated and integrated process. Researches have indicated the wound healing effects of calcium channel blockers in animal models in recent years. Objectives: The aim of this study was to evaluate the wound-healing activity of amlodipine as a calcium channel blocker and combination of amlodipine with phenytoin on excisional cutaneous wound models in rabbit. Materials and Methods: Animals were divided into 5 groups (n = 5). The control group was treated topically with eucerin. The untreated control group received no healing agent. The reference standard group was treated with phenytoin1%. A treatment group was treated with amlodipine 1%. The last group was treated with combination of amlodipine1% and phenytoin 1%. Results: Results indicated significant difference between days needed for complete healing in both of the treatment groups. Wound closure was completed on 13th day and 9th day in amlodipine and combination groups respectively. Conclusions: In conclusion, calcium channel blockers can be used to enhance wound healing, especially if this treatment becomes with phenytoin. Further studies are needed to find out the mechanism of this healing effect.

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Plasma and Gingival Crevicular Fluid Phenytoin Concentrations as Risk Factors for Gingival Overgrowth

Abstract: This study showed that plasma phenytoin level appeared to be a risk factor for phenytoin-induced gingival overgrowth.

Cited by 20 publications

References 53 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

Phenytoin in the Treatment of Osmophobia in Migraine Patient: A Case Report

Wound Healing Potential of Topical Amlodipine in Full Thickness Wound of Rabbit

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