Morphological evaluation of combined effects of cyclosporin and nifedipine on gingival overgrowth in rats

Abstract

It has previously been shown that, while cyclosporin A (CsA) and nifedipine both cause gingival overgrowth in the rat, the combined use of these drugs increases the severity of overgrowth. The aim of this study was to describe the histometry and densities of fibroblasts, collagen fibers and vessels in the gingival tissue of rats that were treated with CsA and nifedipine, either alone or in combination. Rats were treated for 60 days with a daily subcutaneous injection of 10 mg/kg body weight of CsA and/or with 50 mg/kg body weight of nifedipine added to the chow. The results confirmed that CsA causes a more severe overgrowth than nifedipine, and that the combined use of these drugs increases the overgrowth severity. All the rat groups that were studied showed that, as the severity of overgrowth increased, there was a parallel increase in fibroblasts and collagen, and a decrease in vessel content. Therefore, independently of whether the gingival overgrowth was caused by CsA alone, nifedipine alone, or both treatments in combination, the fibroblast and collagen density increased in parallel with the severity of the overgrowth.

Evaluation of gingival alterations in rats medicated with cyclosporine A, tacrolimus and sirolimus: a stereological study

“…Our histomorphometric and stereological results showed that no signs of gingival overgrowth were found in the group administered sirolimus alone, whereas prominent gingival overgrowth was found in groups administered cyclosporine A alone and tacrolimus alone. Many clinical and experimental studies reported that combined drug usage caused much more gingival overgrowth compared with the usage of each drug alone . In contrast to these studies, the results of the present study showed that gingival overgrowth was more prominent in groups administered cyclosporine A and tacrolimus alone compared with combination groups.…”

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

“…In accordance with the macroscopic examination, the histometric findings showed that epithelial thickness and connective tissue width were increased in groups 5, 6, and 7 and connective tissue height was increased in groups 5 and 7, where remarkable gingival overgrowth was observed. These results are consistent with previous findings that showed increased thickness of epithelium and connective tissue 6,22 . Those authors also reported increases in the density of fibroblasts and collagen fibers.…”

“…Immunosuppressive agents and calcium channel blockers are used together to treat post‐transplant high blood pressure and decrease nephrotoxicity 20 . In many clinical studies, combined use of nifedipine and tacrolimus in transplant patients was reported to cause more severe gingival overgrowth than nifedipine or tacrolimus alone 5,8,10,11,21‐24 …”

Effect of azithromycin on gingival overgrowth induced by cyclosporine A + nifedipine combination therapy: A morphometric analysis in rats

“…This observation is in accordance with the earlier studies. [10141522] In one of the recent experimental studies using the rat model, authors reported DIGO only after 24 weeks of administration of tacrolimus and Nf, alone or in combination. [23] Differences of drug doses were accounted as the possible reason for such variation in findings.…”