The relationship of 5,5-diphenylhydantoin metabolism to the species-specific induction of gingival hyperplasia in the rat

Conard, Gordon J.; Haavik, Coryce O.; Finger, Kenneth F.

doi:10.1016/0003-9969(72)90214-2

Cited by 12 publications

(4 citation statements)

References 7 publications

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“…In the present study, we have investigated the formation of reactive metabolite of DPH and its covalent binding with gingival proteins in the rat as a possible model for the biochemical mechanism for PIGO. Although rats have remained resistant to PIGO (Conard, Haavik & Finger 1972), they have been used extensively to assess metabolic activation and tissue binding of drugs in general (Mitchell et al 1973, Rao, Krishna & Gillette 1975, Rao 1977.…”

mentioning

confidence: 99%

Metabolic activation and covalent binding of phenytoin in the rat gingiva

Wortel

Hefferren

Rao

1979

J of Periodontal Research

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confidence: 99%

Metabolic activation and covalent binding of phenytoin in the rat gingiva

Wortel

Hefferren

Rao

1979

J of Periodontal Research

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“…The exact pathogenesis of PGO remains unclear; however, it is suggested that PHT and its metabolites exert a direct effect on gingival tissues 2 22. Other less accepted hypotheses include immunosuppression of long-term PHT, alteration in the metabolism of adrenal glands leading to adrenal–cortical unresponsiveness, stimulation of sodium pump acting as a stimulus of fibroblasts and folic acid depletion, increased sulfated glycosaminoglycans, gingival phenotype population differences, reduced collagen activity and disruption of fibroblast cellular Na + /Ca ++ flux.…”

Section: Discussionmentioning

confidence: 99%

Phenytoin-induced severe gingival overgrowth in a child

et al. 2014

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Gingival enlargement or overgrowth (GO) is a common complication of the anticonvulsant drug phenytoin (PHT). GO is evident in almost half of the patients receiving PHT therapy. PHT-induced gingival overgrowth (PGO) is more common in children than in adults and affects both males and females equally. PGO may vary from mild to severe and does not seem to be dose dependant. It is supposed that PHT and its metabolites cause a direct effect on the periodontal tissues; however, poor oral hygiene may contribute to the severity of gingival inflammation in patients with PGO. Management of PGO includes meticulous oral hygiene practice to reduce inflammation and surgical excision of the overgrown tissue, known as gingivectomy. We present a case of PHT-induced severe GO in a 10-year-old boy and discuss the clinical features, aetiology, pathogenesis and management of PGO.

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“…The short plasma half-life of PHT in the rat compared to man suggested the possibility that failure to produce gingival overgrowth in the rat may be the result of its rapid metabolism and the disappearance of PHT from the plasma (33).…”

Section: Discussionmentioning

confidence: 99%

Establishment of Rat Model of Drug-Induced Gingival Overgrowth Induced by Continuous Administration of Phenytoin

Tamamori¹,

Tamura²,

Yamazaki³

et al. 2005

J Pharmacol Sci

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Abstract. It is well-known that the anticonvulsant drug, phenytoin (PHT), induces gingival overgrowth as a side effect. The mechanism of PHT-induced gingival overgrowth, however, is not well understood. One reason for this is the lack of an adequate animal model for the PHT-induced gingival overgrowth. The purpose of this study was to establish a rat model of the drug-induced gingival overgrowth. Fourteen-day-old rats were randomly divided into 3 groups (5 rats / group). The control rats received only the vehicle. The rats in the experimental group were injected with 50 mg / kg per day (group L) and 100 mg / kg per day (group H) of PHT. They received a subcutaneous injection of vehicle or PHT twice a day for 42 days. A charge-coupled device (CCD) laser displacement sensor was used for measurement of the severity of gingival overgrowth of the mandibles. There was no significant difference in the growth of rats between the PHT-injected and the control groups. The CCD laser displacement sensor can measure minute changes in the gingival overgrowth in rats, and a significant extension of the buccal gingiva was observed in groups L and H. Using the CCD sensor, it is possible to quantify the change in the gingiva under precise control of the PHT dose.

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The relationship of 5,5-diphenylhydantoin metabolism to the species-specific induction of gingival hyperplasia in the rat

Cited by 12 publications

References 7 publications

Metabolic activation and covalent binding of phenytoin in the rat gingiva

Metabolic activation and covalent binding of phenytoin in the rat gingiva

Phenytoin-induced severe gingival overgrowth in a child

Establishment of Rat Model of Drug-Induced Gingival Overgrowth Induced by Continuous Administration of Phenytoin

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