Diltiazem did not induce gingival overgrowth in rats: a clinical, histological and histometric analysis

Abstract

The administration of calcium channel blockers has been associated with gingival overgrowth. However, there are few studies in humans or animals that evaluated the effect of diltiazem on gingival tissues. The present study assessed the influence of diltiazem, at different dosages and treatment duration, on gingival tissues of rats, using clinical, histological and histometric analyses. Eighty young male rats were separated into eight groups according to the dosage and duration of treatment. Rats were treated for 20 or 40 days with a daily subcutaneous injection of 5, 20 or 50 mg/kg of body weight of diltiazem. The results confirmed that diltiazem did not induce gingival overgrowth in rats. For all animals, the evaluation did not show gingival alterations regardless of the dosages and periods of treatment. The histometric analysis showed no significant change in the area of epithelium and connective tissues, although after 40 days of treatment a decrease in the area of connective tissue was observed, without statistically significant difference from control groups. Within the limits of this study, we suggest that diltiazem did not induce gingival overgrowth.

Influence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats

“…In fact, the fi ndings of previous investigations have shown that the administration of diltiazem in the doses used in the present study did not induce toxicity and that the treatment was well supported by the animals. 8,13,16,17 Macroscopically, the sucrose-rich diet induced dental biofi lm accumulations in all animals though none of them exhibited clinical characteristics of gingival overgrowth, which confi rms our previous fi ndings. 8 However, Morisaki et al 16 (2000) observed gingival overgrowth in rats after administration of diltiazem in doses greater than those used in the present study during a similar experimental period.…”

“…8,13,16,17 Macroscopically, the sucrose-rich diet induced dental biofi lm accumulations in all animals though none of them exhibited clinical characteristics of gingival overgrowth, which confi rms our previous fi ndings. 8 However, Morisaki et al 16 (2000) observed gingival overgrowth in rats after administration of diltiazem in doses greater than those used in the present study during a similar experimental period. Microscopically, there was only a mild infl ammation in the animals (Figure 1), which is particularly relevant because the diet followed by the animals was expected to cause gingivitis.…”

“…8 At the same time, it has been suggested that drug-induced gingival overgrowth is related to factors such as treatment duration, presence of bacterial biofi lm and gingival infl ammation. 9,10 Therefore, our hypothesis was to explore in rats treated with diltiazem whether gingival infl ammation, secondary to a sucrose-rich diet, would induce gingival alterations.…”

“…8 Briefl y, the slides were selected in a standardized manner, representing the initial, intermediate and fi nal portions of the gingival margin, thus totalizing 10 readings of histological sections at 60-μm intervals for each animal. The histometric analysis was performed using a DIASTAR optical microscope (Leica Reichert & Jung Products, Wetzlar, Germany) with an objective lens 10/0.25 adapted to a video camera (Sony DXC -107A, Sony Electronics Inc., Shinagawa-ku, Tokyo, Japan) and connected to a computer.…”

“…2,3 On the other hand, there are few reports of diltiazeminduced gingival overgrowth in humans. [4][5][6][7] The fi ndings of a recent study 8 showed that in rats with noninfl amed gingival tissue, diltiazem did not induce gingival overgrowth. Nevertheless, the pathogenesis of drug-induced gingival enlargement is uncertain and confl icting and has been related to several factors, namely age, gender, treatment duration, plasmatic and salivary drug concentration, presence of bacterial biofi lm, gingival tissue infl ammation, genetics and synergism with other medicaments.…”