Phenytoin-Mediated Androgen Metabolism in Gingival Fibroblasts

The study investigated the effects of the alkaline phosphatase inhibitor levamisole and the antiandrogen finasteride on 5α-reductase activity in gingival fibroblasts to understand phenytoin-induced gingival overgrowth. Human gingival fibroblasts were treated with phenytoin, levamisole, and finasteride, alone and in combination, and analyzed for steroid metabolites. Phenytoin increased DHT synthesis by 1.7-fold, while finasteride and levamisole inhibited it by 1.8-fold and 34%, respectively. The combination of phenytoin with finasteride or levamisole significantly reduced DHT synthesis compared to phenytoin alone. The results suggested that levamisole and finasteride could effectively decrease DHT production in fibroblasts, offering a potential approach to mitigate phenytoin-induced gingival overgrowth.