Effects of long-term cyclosporin therapy on gingiva of rats: analysis by stereological and biochemical estimation

Abstract

Cyclosporin A (CsA) is used as an immunosuppressive agent and its prominent side effect is the induction of gingival overgrowth, which remains a significant problem. The risk factors appraised include the duration of treatment. However, there are no stereological and biochemical studies exploring the effects of long-term CsA therapy on gingival tissue. The purpose of the present study was to investigate the level of TGF-beta1 in saliva and describe the densities of fibroblasts and collagen fibers in the gingival tissue of rats treated with CsA for long periods. Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg of body weight of CsA. At the end of the experimental periods, saliva was collected for the determination of TGF-beta1 levels. After histological processing, the oral epithelium and the connective tissue area were measured as well as the volume densities of fibroblasts (Vf) and collagen fibers (Vcf). After 60 and 120 days of CsA treatment, there was a significant increase in Vf and Vcf as well as a significant increase in TGF-beta1 levels. After 180 and 240 days, reduction in the gingival overgrowth associated with significant decreases in the level of TGF-beta1, and also decreased Vf and Vcf, were observed. The data presented here suggest that after long-term therapy, a decrease in TGF-beta1 levels occurs, which might contribute to an increase in the proteolytic activity of fibroblasts in the gingiva, favoring the normality of extracellular matrix synthesis.

Local Inflammation Exacerbates Cyclosporine A-Induced Gingival Overgrowth in Rats

“…Spolidorio et al reported that the TGF-β1 level in saliva was significantly higher at 60 and 120 days of treatment with CsA when compared with control groups [28]. In agreement with the previous study, our study depicted a significant increase in serum TGF-β1 levels in groups treated with CsA compared to groups without CsA treatment.…”

“…The enlargement appeared within 9 weeks of CsA dosing, similar to the observations made in other studies [26,[28][29][30].…”

Immunohistochemical Analysis of Cell Proliferation and Bcl-2 Expression in Drug-Induced Gingival Overgrowth

“…The high percentage of cases of DIGO exhibiting intense collagenization (90%) observed in the present study agrees with the results of other studies suggesting that the development GO involves alterations in fibroblast metabolism represented by an increased secretory activity of ECM components and/or a reduction in the secretion of matrix metalloproteinases [2,14,22]. Within this context, there is evidence indicating that the cellular and molecular characteristics of DIGO might vary as a function of the drug used [23].…”

The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats – a morphological evaluation

“…In contrast to the present findings, it has been recently demonstrated that after brief periods of treatment with CsA, gingival overgrowth was associated with a significant increase in epithelium and connective tissue. After 180 and 240 days of treatment, there was a reduction in gingival overgrowth with significant decreases in the epithelium and the connective tissue (Spolidorio et al , 2005). These results are in agreement with a prospective longitudinal study (Montebugnoli et al , 2000) that showed a relevant role of time in reducing gingival overgrowth in heart transplanted patients undergoing CsA therapy from 6 to 18 months after transplantation.…”