Drug-induced
gingival overgrowth is caused by the antiseizure medication
phenytoin,
calcium channel blockers, and
ciclosporin. Characteristics of these
drug-induced
gingival overgrowth lesions differ. We evaluate the ability of a mouse model to mimic human
phenytoin-induced
gingival overgrowth and assess the ability of a
drug to prevent its development.
Lovastatin was chosen based on previous analyses of tissue-specific regulation of CCN2 production in human gingival fibroblasts and the known roles of CCN2 in promoting
fibrosis and epithelial to mesenchymal transition. Data indicate that anterior gingival tissue overgrowth occurred in
phenytoin-treated mice based on gross tissue observations and histomorphometry of tissue sections. Molecular markers of epithelial plasticity and
fibrosis were regulated by
phenytoin in gingival epithelial tissues and in connective tissues similar to that seen in humans.
Lovastatin attenuated epithelial gingival tissue growth in
phenytoin-treated mice and altered the expressions of markers for epithelial to mesenchymal transition. Data indicate that
phenytoin-induced
gingival overgrowth in mice mimics molecular aspects of human
gingival overgrowth and that
lovastatin normalizes the tissue morphology and the expression of the molecular markers studied. Data are consistent with characterization of
phenytoin-induced human
gingival overgrowth in vivo and in vitro characteristics of cultured human gingival epithelial and connective tissue cells. Findings suggest that
statins may serve to prevent or attenuate
phenytoin-induced human
gingival overgrowth, although specific human studies are required.