Phenytoin and gingival mucosa: A molecular investigation

Int J Immunopathol Pharmacol. 2019 Jan-Dec:33:2058738419828259. doi: 10.1177/2058738419828259.


Several distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers, caused gingival overgrowth. One of the main drugs associated with the gingival overgrowth is the anti-epileptic such as phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. In our study, we evaluate the effect of phenytoin, a drug whose active substance is phenytoin, on gingival fibroblasts of healthy volunteers. Gene expression of 29 genes was investigated in gingival fibroblasts' cell culture treated with phenytoin compared with untreated cells. Among the studied genes, only 13 genes (CXCL5, CXCL10, CCR1, CCR3, CCR5, CCR6, IL-1A, IL-1B, IL-5, IL-7, IL-6R, BMP-2, and TNFSF-10) were statistically significant. All but one gene resulted downregulated after 24 h of treatment with phenytoin. BPM2 was the only, although weakly, up-expressed gene. Probably, we have not highlighted overexpression of the other inflammatory molecules because the study was performed on healthy people. Many studies show that phenytoin induces the overexpression of these cytokines but, probably, in our study, the drug does not have the same effect because we used gingival fibroblasts of healthy people.

Keywords: anti-epileptic drug (AED); gene expression; gingival hyperplasia; phenytoin.

MeSH terms

  • Adult
  • Aged
  • Anticonvulsants / adverse effects*
  • Cells, Cultured
  • Child
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Gingiva / drug effects*
  • Gingiva / metabolism
  • Gingival Overgrowth / chemically induced*
  • Gingival Overgrowth / metabolism
  • Healthy Volunteers
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Male
  • Phenytoin / adverse effects*
  • Up-Regulation / drug effects
  • Young Adult


  • Anticonvulsants
  • Cytokines
  • Phenytoin