An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth

Farook, Fathima Fazrina; Nizam, Mohamed Nuzaim Mohamed; Alshammari, Abdulsalam

doi:10.2174/1874210601913010430

Cited by 9 publications

(8 citation statements)

References 65 publications

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“…Gingival overgrowth is claimed to be associated with certain antiseizure, immunosuppressive, or antihypertensive drug therapies 5 . However, the molecular and cellular mechanisms underlying to this observation are still unclear 29,30 . Data available until now highlight this phenomenon as occurring with phenytoin and valproic acid, while our observations concern many antiseizure drugs.…”

Section: Discussionmentioning

confidence: 70%

Gingival overgrowth induced by anticonvulsant drugs: A cross‐sectional study on epileptic patients

Gallo

Bonvento

Zagotto

et al. 2020

J of Periodontal Research

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Objective Our aim was to estimate the prevalence of gingival overgrowth (hyperplasia) and to determine whether active molecules affect the severity of overgrowth in a group of epileptic patients. Background The effects of phenytoin on oral health have been explored in different studies, yet little information is available on other antiepileptic drugs. Methods Data were collected from 213 subjects of both sexes, from 5 to 80 years. Patients taking the same antiepileptic therapy for at least 1 year and meeting the inclusion criteria of the study (n = 162) were subjected to measurement of gingival overgrowth according to the modified Harris and Ewalt classification and O’Leary's plaque control record (OLR). Descriptive statistics were calculated. Data were analyzed using Pearson's r correlation coefficient and chi‐square test. Significance level was set at 5%. Results The active drugs lamotrigine, oxcarbazepine, and phenobarbital were significantly associated with gingival overgrowth in 61%, 71%, and 53% of cases, respectively, and phenytoin, valproic acid, and carbamazepine in 50%, 44%, and 32% of cases, respectively. Conclusion Different antiepileptic molecules may be related to gingival overgrowth. In addition to phenytoin, also lamotrigine, oxcarbazepine, and phenobarbital were associated with increased prevalence of gingival overgrowth. In the management of epileptic patients, dentists should take into account different drugs as possible causes for gingival overgrowth and warn for possible alternatives.

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Section: Discussionmentioning

confidence: 70%

Gingival overgrowth induced by anticonvulsant drugs: A cross‐sectional study on epileptic patients

Gallo

Bonvento

Zagotto

et al. 2020

J of Periodontal Research

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“…Gingiva recession is one of the common oral diseases, and the decrease of proliferation and function of hGFs are an important reason of gingiva recession 26,27 . The aging of hGFs is an important reason for the decline of cell repair ability and anabolic ability, while phenytoin can stimulate the proliferation and anabolic ability of hGFs 28‐30 . In this study, we found that phenytoin can be used as a potential drug to interfere with hGFs aging in vitro.…”

Section: Discussionmentioning

confidence: 71%

Phenytoin sodium‐ameliorated gingival fibroblast aging is associated with autophagy

Kang

Yang

Wei

et al. 2020

J of Periodontal Research

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Background and Objective Human gingival fibrolasts aging is an important cause of periodontal disease. Phenytoin sodium (phenytoin) has a side effect of gingival hyperplasia and an effect on the autophagy progress. This study investigated whether the effect of phenytoin on aging gingival fibroblast is related to the autophagy pathway. Material and Methods The aging model of gingival fibroblast cell line HGF‐1 was induced by hydrogen peroxide (H2O2), and the treatment of phenytoin and 3‐methyladenine (3‐MA) was performed simultaneously. Cell viability, cell cycle, and intracellular calcium ion were measured by flow cytometry. Changes in expression of basic fibroblast growth factor (bFGF), P16INK4A, P21cip1, and bFGF, P16INK4A, P21cip1, LC3II, p62, and Beclin were tested by using reverse transcription polymerase chain reaction, western blot, and immunofluorescence staining. Results The results showed that aging HGF‐1 proliferation was inhibited by H2O2, gene, protein expression of bFGF, P16INK4A, and P21cip1 were decreased, autophagy‐related proteins LC3II, p62, and Becline were decreased, and the proportion of G0/G1 phase and intracellular calcium ion of cell cycle was increased. Phenytoin treatment could recovery above changes, but the effect of phenytoin could be blocked by 3‐MA. Conclusion We propose that phenytoin alleviates the aging of gingival fibroblasts induced by H2O2. This condition is related to the enhancement of autophagy pathway.

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“…They showed that these substances have a special effect on further reducing total protein and collagen. Also, fibroblasts obtained from patients with increased volume due to phenytoin consumption show an increase in the synthesis of sulfated glycosaminoglycan in vitro (11).…”

Section: Resultsmentioning

confidence: 97%

“…In this study, only one aspect of regeneration, namely cell proliferation, has been addressed, and the issue of cell differentiation and production of extracellular material has not been investigated. Some studies have shown that phenytoin indirectly increases collagen by reducing the ability of the extracellular matrix to degrade (especially by cathepsin L) and by producing a type of inactive fibroblastic collagen, thereby increasing tissue volume (11,18). This aspect of regeneration should also be considered to determine the effect of phenytoin on the extracellular matrix of extracellular PDL fibroblasts (19).…”

Section: Resultsmentioning

confidence: 99%

The effect of phenytoin on the proliferative ability of periodontal and gingival ligament fibroblasts in cell culture medium

Qi¹,

Peng²,

Deng³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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Periodontal ligament fibroblasts (PDLFs) play a vital role in the period of periodontal regeneration. In addition, studies show that diphenylhydantoin (phenytoin) increases the growth of gingival fibroblasts. If this effect is also present in the periodontal ligament (PDL) fibroblasts, it may be used to regenerate periodontal tissues. Accordingly, this study aimed to compare the effect of phenytoin on the growth rate of gingival fibroblast cells and PDL in the cell culture medium. In this regard, 10 Wistar rats were selected. The gingival specimen was obtained from the area between the upper teeth, and the PDL specimen was obtained from the middle third of the lower teeth root. After transferring the samples to a suitable culture medium for culturing PDL and gingival fibroblasts, each sample was divided into two experimental and control groups. In the experimental group, 20 mg/ml phenytoin dissolved in sodium hydroxide was added to Dulbecco's modified Eagle's medium (DMEM). After 48 hours, fibroblast cell proliferation was assessed through a 1-WST cell proliferation kit by ELISA. The proliferation of gingival fibroblast cells and PDL in both test and control groups were statistically analyzed by the independent t-test. The results showed that the effect of phenytoin on the proliferation of gingival fibroblast cells and PDL fibroblast cells is significant. Also, the proliferation of PDL cells was significantly different from gingival cells in the experimental group (P <0.001) and was higher in PDL cells. In general, in this study, it was found that phenytoin in vitro, like in vivo, is able to increase the proliferation of gingival fibroblast cells, and this phenytoin effect is also present in PDL fibroblast cells.

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An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth

Cited by 9 publications

References 65 publications

Gingival overgrowth induced by anticonvulsant drugs: A cross‐sectional study on epileptic patients

Gingival overgrowth induced by anticonvulsant drugs: A cross‐sectional study on epileptic patients

Phenytoin sodium‐ameliorated gingival fibroblast aging is associated with autophagy

The effect of phenytoin on the proliferative ability of periodontal and gingival ligament fibroblasts in cell culture medium

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