Drug-Induced Gingival Overgrowth: A Pilot Study on the Effect of Diphenylhydantoin and Gabapentin on Human Gingival Fibroblasts

Int J Environ Res Public Health. 2020 Nov 7;17(21):8229. doi: 10.3390/ijerph17218229.

Abstract

Introduction: The administration of several classes of drugs can lead to the onset of gingival overgrowth: anticonvulsants, immunosuppressants, and calcium channel blockers. Among the anticonvulsants, the main drug associated with gingival overgrowth is diphenylhydantoin.

Materials and methods: In this study, we compared the effects of diphenylhydantoin and gabapentin on 57 genes belonging to the "Extracellular Matrix and Adhesion Molecule" pathway, present in human fibroblasts of healthy volunteers.

Results: Both molecules induce the same gene expression profile in fibroblasts as well as a significant upregulation of genes involved in extracellular matrix deposition like COL4A1, ITGA7, and LAMB3. The two treatments also induced a significant downregulation of genes involved in the expression of extracellular matrix metalloproteases like MMP11, MMP15, MMP16, MMP24, and transmembrane receptor ITGB4.

Conclusions: Data recorded in our study confirmed the hypothesis of a direct action of these drugs at the periodontium level, inducing an increase in matrix production, a reduction in its degradation, and consequently resulting in gingival hyperplasia.

Keywords: antiepileptic drug (AED); diphenylhydantoin; drug-induced gingival hyperplasia (DIGH); gabapentin; gingival hyperplasia.

MeSH terms

  • Aged
  • Anticonvulsants / adverse effects*
  • Child
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gabapentin / adverse effects*
  • Gene Expression / drug effects
  • Gingiva / drug effects*
  • Gingiva / metabolism
  • Gingiva / pathology
  • Gingival Hyperplasia / chemically induced*
  • Gingival Overgrowth / chemically induced*
  • Gingival Overgrowth / metabolism
  • Healthy Volunteers
  • Humans
  • Male
  • Phenytoin / adverse effects*
  • Pilot Projects
  • Up-Regulation / drug effects
  • Young Adult

Substances

  • Anticonvulsants
  • Phenytoin
  • Gabapentin