Basic Study on Medication for Gingival Overgrowth

Objectives: Gingival overgrowth, a disease involving aesthetic and functional loss, is caused by phenytoin (PHT), cyclosporine, nifedipine, etc. Particularly, an incidence of PHT-induced gingival overgrowth is high probability. It has been reported that one of the mechanism of PHT-induced gingival overgrowth was the apoptosis inhibition in gingival fibroblasts. We demonstrated that 18-alpha-glycyrrhetinic acid (18α-GA) induced the apoptosis in gingival fibroblasts obtained from the patients of nifedipine-induced gingival overgrowth in the past. In this study, we investigated the effects of 18α-GA on the apoptosis of gingival fibroblasts exposure to PHT.
Methods: Gingival fibroblasts were cultured in DMEM supplemented with 10% serum to reach the semi-confluent and then cells were stimulated in serum-free DMEM with or without (control) only PHT or PHT+18α-GA for the periods as shown below. On day 0, 7, 14, 21 after stimulation, the relative number of apoptotic cells was determined by ELISA, and the rates to the value of day 0 were caliculated at each time point. On day 0 and 21 after stimulation, the numbers of viable cells were counted and the rates to the value of day 0 were calculated at day 21.
Results: Number of apoptotic cells was increased in the control group with passage of time, however, PHT significantly decreased that of apoptotic cells at all time points compared to the control. 18α-GA significantly increased the apoptotic cell numbers on day 14 and 21 compared to the PHT group. Also, 18α-GA significantly decreased the rate of viable cells on day 21 in the gingival fibroblasts exposed to PHT compared to the PHT group.
Conclusions: In the present study, it was shown that 18α-GA induced the apoptosis in the gingival fibroblasts exposed to PHT. 18α-GA may be applied for the medication of gingival overgrowth.