Long-term effects of nifedipine on human gingival epithelium: a histopathological and immunohistochemical study

Abstract

The chronic usage of nifedipine is associated with the appearance of gingival overgrowth (GO). The frequency of GO associated with chronic nifedipine therapy remains controversial and the possible subclinical effects of this drug on the gingival epithelium should be investigated. We investigated the epithelial proliferation index and apoptosis rate, and their association with epithelial enlargement. Proliferation (Ki67 and Cyclin B1) and apoptosis (BCL2, Bax and p53) markers were identified by immunohistochemistry in twenty-one samples of gingival tissue from patients undergoing chronic treatment with nifedipine and in eleven samples of gingival tissue from healthy patients who did not use drugs associated with GO (control). Our results show that the epithelial tissue of nifedipine users has considerably longer rete pegs compared to control (P = 0.01). However, the density of Ki67(+) and Cyclin B1(+) cells was similar in both groups. Regarding apoptosis, we found more BCL2(+) cells in the nifedipine group when compared to controls (P = 0.12). An increase in Bax(+) cells in the nifedipine group compared to control (P = 0.003) was also seen, and slightly lower levels of p53(+) expression were observed (P = 0.51). Our results suggest that the chronic use of nifedipine is not associated with subclinical changes in gingival tissue.

Effects of Tacrolimus and Nifedipine, Alone or in Combination, on Gingival Tissues

“…The expression of proliferation cell nuclear antigen, one of the most popular proliferation markers, was found to be increased in drug‐induced gingival overgrowth 29,52 . More recently, an increase in mitotic activity as measured by the expression of Ki67 and cyclin‐B1 proliferation markers was found in drug‐induced gingival overgrowth 14,53 . On the other hand, Shimizu et al 43 reported that epithelial hyperplasia in nifedipine‐induced gingival overgrowth is induced not by an increase in proliferation but by the prolongation of cell life through inhibition of apoptosis.…”

“…Nifedipine, a dihydropyridine, is a calcium channel blocker that is widely used to treat ischemic cardiovascular diseases such as hypertension, angina pectoris, and ventricular arrhythmias 13,14 . Unlike tacrolimus, nifedipine is well documented to induce gingival overgrowth as a side effect.…”

“…The balance between cell proliferation and apoptosis may be the characteristic of different forms of gingival overgrowth, and variations in this balance may provide insights into different etiologies in different forms of gingival overgrowth 26 . Therefore, recent studies have focused on the role of markers of severe proliferation and apoptosis 14,27‐29 …”

Influence of 3 calcium channel blockers on gingival overgrowth in a population of severe refractory hypertensive patients

“…Gingival overgrowth is a common adverse effect associated with the continued use of some classes of drugs . In this context, nifedipine (dihydropyridine), which is still the most widely used calcium channel blocker (CCB) in many countries, amlodipine and other drugs such as felodipine and verapamil have been associated with gingival overgrowth …”

Analysis of thermochemotherapy-induced apoptosis and the protein expressions of Bcl-2 and Bax in maxillofacial squamous cell carcinomas

“…The mean of stained cells was obtained by dividing the number of positive cells by the total area (0.0961 mm 2 ). All measurements were made by the same examiner following calibration [16].…”