PATHOGENESIS OF DRUG-INDUCED GINGIVAL OVERGROWTH - A REVIEW OF STUDIES IN THE RAT MODEL

DRUG-INDUCED GINGIVAL OVERGROWTH is a side effect associated principal ly with 3 types of drugs: anticonvulsant (phenytoin), immunosuppressan t (cyclosporine A), and various calcium channel blockers (nifedipine, verapamil, diltiazem). In this review, we describe the features of phe nytoin-, cyclosporine A- and nifedipine-induced gingival overgrowth in rats and discuss factors influencing the onset and severity of these disorders. There are several features common to the gingival overgrowt h induced by these drugs: 1) gingival overgrowth is more conspicuous i n the buccal than in the lingual gingiva and less severe in the maxill a than in the mandible; 2) once the blood concentration of the drug re aches a certain level as a result of increasing the dose, the incidenc e of gingival overgrowth is 100% and its severity is dependent on the blood level, the most severe overgrowth being induced by cyclosporine A; 3) the duration of drug administration for maximal gingival overgro wth to develop is about 40 days; 4) the gingival overgrowth regresses spontaneously after discontinuing the drug; 5) accumulation of dental plaque is not essential for the onset of overgrowth, but plays a role in its severity; and 6) more severe overgrowth is induced in young tha n in old rats. Furthermore, male rats are more susceptible than female s to nifedipine-induced gingival overgrowth. These results suggest tha t drug-induced gingival overgrowth in rats is dependent on the oral dr ug dose, blood drug level, age, and sex and that preexisting gingival inflammation is a factor relevant to its severity. Since these factors have also been suggested to be important determinants for human drug- induced gingival overgrowth, the rat model may prove valuable in the f uture for elucidating the molecular pathogenesis of the disorder.