Pathogenesis of drug-induced gingival overgrowth. A review of studies in the rat model.
Drug-induced gingival overgrowth is a side effect associated principally with 3 types of drugs: anticonvulsant (phenytoin), immunosuppressant (cyclosporine A), and various calcium channel blockers (nifedipine, verapamil, diltiazem). In this review, we describe the features of phenytoin-, 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 overgrowth induced by these drugs: 1) gingival overgrowth is more conspicuous in the buccal than in the lingual gingiva and less severe in the maxilla than in the mandible; 2) once the blood concentration of the drug reaches a certain level as a result of increasing the dose, the incidence 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 overgrowth 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 than in old rats. Furthermore, male rats are more susceptible than females to nifedipine-induced gingival overgrowth. These results suggest that drug-induced gingival overgrowth in rats is dependent on the oral drug 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 future for elucidating the molecular pathogenesis of the disorder.
Nishikawa
S
S
Department of Periodontology and Endodontology, Tokushima University School of Dentistry, Japan.
Nagata
T
T
Morisaki
I
I
Oka
T
T
Ishida
H
H
D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000633:toxicity*; D002121:Calcium Channel Blockers / Q000097:blood / Q000633:toxicity*; D016572:Cyclosporine / Q000097:blood / Q000633:toxicity*; D003773:Dental Plaque / Q000150:complications; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005885:Gingival Hyperplasia / Q000139:chemically induced* / Q000209:etiology; D005891:Gingivitis / Q000150:complications; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000633:toxicity*; D008297:Male; D009543:Nifedipine / Q000097:blood / Q000633:toxicity*; D010672:Phenytoin / Q000097:blood / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013047:Specific Pathogen-Free Organisms
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D010672:Phenytoin; D016572:Cyclosporine; D009543:Nifedipine