Effect of concomitant administration of nifedipine and tacrolimus on the development of gingival overgrowth in rats

Abstract

Background/purpose: It is still controversial whether tacrolimus can induce gingival overgrowth. Calcium channel blockers of nifedipine are commonly used for lessening the side effect of high blood pressure induced by tacrolimus; however, nifedipine can also induce gingival overgrowth. This study was conducted to evaluate the effect of concomitant administration of nifedipine and tacrolimus on gingival overgrowth in rats. Materials and methods: Thirty-six Sprague-Dawley rats were assigned into four groups, including a control group. In drug groups, either tacrolimus (1.5 mg/kg) or nifedipine (30 mg/kg), or both drugs together were administrated daily for 6 weeks. The gingival morphology was examined macroscopically on the mandibular central papilla from cast models biweekly, and analyzed by measuring the sulcular probing depth and the keratinized gingival width around the first mandibular molars immediately after sacrificing. By histology, changes of papillae, including the connective tissue, and the epithelial and total tissue areas, were measured at two different tissue levels. Results: Significant increases in papillary dimensions, including depth, width, and height, were observed across all groups after Week 1, with the control group showing less changes than experimental drug groups. Among drug groups, significantly increased papillary dimensions were noted in the nifedipine group when compared with groups treated with tacrolimus and both drugs. Changes in keratinized gingival width were found to be similar in the tacrolimus and combined-drug groups but greater in the nifedipine group. For probing depth, experimental groups showed greater changes than the control group, but no difference was observed among the experimental groups. Similar trends were presented for the total and connective tissue areas; however, the epithelial tissue areas did not show any difference among the four treatment groups. Conclusion: Gingival overgrowth could be induced either by nifedipine or by tacrolimus, although the extent of gingival overgrowth induced by tacrolimus would be less than that by nifedipine. However, a concomitant administration of nifedipine and tacrolimus did not aggravate the induced gingival overgrowth.

Keywords

• gingival
• nifedipine
• overgrowth
• rat
• tacrolimus