Factors influencing nifedipine-induced gingival overgrowth in rats
Nifedipine, a calcium channel blocker, is associated with gingival overgrowth. Specifically, this laboratory study using rats was designed to investigate the relationship between the nifedipine concentration in the diet and that in serum; to evaluate the effects of the drug concentration in serum and the duration of drug administration on the degree of gingival overgrowth; to demonstrate regression of the gingival overgrowth after withdrawal of nifedipine; and to determine differences in age or sex on gingival overgrowth. Male and female rats aged 20, 50, and 90 days were used. To examine the dose-response effect of dietary nifedipine on the levels in serum and gingival overgrowth, as well as sex dependency of the drug action, male and female rats were divided into five groups. The rats were fed a diet containing various concentrations of nifedipine (50 to 250 mg/kg) for 55 days; controls were given the same diet without the drug. To evaluate the duration of drug administration, male rats were divided into seven groups, given a diet containing nifedipine at 250 mg/kg, and sacrificed on days 0,10, 20, 30, 40, 55, and 70 for assessment of gingival overgrowth. To evaluate the effects of drug withdrawal, a diet containing nifedipine 250 mg/kg was replaced with a drug-free diet from day 30 onward; gingival overgrowth was assessed on days 55 and 70. Overgrowth was measured using a dissection microscope by specifically observing the soft tissue at the mesial cusp of both the right and left first molars with a 100 um banded probe.
The minimum dietary concentrations of the drug required to elicit gingival overgrowth in males and females were 150 and 100 mg/kg, respectively. The oral administration of nifedipine increased the serum level of the drug in a dose-dependent manner in both sexes. Higher serum levels were required in females to attain the same degree of gingival overgrowth; degree of overgrowth depended on serum concentrations in both sexes. Administration of nifedipine (250 mg/kg) for 20 days was sufficient to induce maximal overgrowth but only for the 20-day-old rats. Gingival overgrowth regressed to normal 40 days after drug cessation.
It appears that nifedipine-induced gingival overgrowth in rats occurs in accordance with the drug concentration in both the diet and serum. Overgrowth was more likely to occur in younger male rats. [D.S.S.]
Ishida, H.,T. Kondoh, M. Kataoka, S. Nishikama, T. Nakagawa, I. Morisaki J. Kido, T. Oka, and T. Nagata, J Periodont, 66:345, 1995