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

Dorina Lauritano, Giulia Moreo, Luisa Limongelli, Elena Tregambi, Annalisa Palmieri and Francesco Carinci
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Dorina Lauritano: Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
Giulia Moreo: Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
Luisa Limongelli: Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy
Elena Tregambi: Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
Annalisa Palmieri: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, via Belmoro 8, 40126 Bologna, Italy
Francesco Carinci: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy

IJERPH, 2020, vol. 17, issue 21, 1-13

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: diphenylhydantoin; gabapentin; antiepileptic drug (AED); gingival hyperplasia; drug-induced gingival hyperplasia (DIGH) (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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