Avaliação do efeito da roxitromicina na regressão da hiperplasia gengival induzida pela Ciclosporina em ratos

Abstract

Gingival overgrowth (GO) is a common side effect of the chronic use of cyclosporine (CsA), an immunosuppressive drug which is widely used to prevent organ rejection in transplant patients. Recent studies have shown elevated levels of specific cytokines in hyperplastic gingival tissue, particularly TGF-ß, which suggests that this growth factor plays a role in the accumulation of extracellular matrix in gingival hyperplasia. Treatment for this complication, until recently, was only surgical. Today, several studies have demonstrated the effectiveness of azithromycin, a macrolide antibiotic, in the regression of this undesirable side effect caused by the immunosuppressant. In this study, an experimental model for assessing the therapeutic effect of roxithromycin in GO was created. We used four groups of mice totaling 32 individuals. GO was induced during five weeks and drug treatment was given on the 6th week as follows: group A – animals received saline; group B – animals received CsA and were treated with saline on the 6th week; group C – animals received CsA and, on the 6th week, ampicilin; and group D – animals received CsA during 5 weeks and, on the 6th week, were treated with roxithromycin. Therefore, this study evaluated the effect of roxithromycin in the treatment of GH. Additionally, we investigated the expression of transforming growing factor beta (TGF- 2) through an immunohistochemical technique (avidin-biotin-peroxidaseantiperoxidase complex) in order to better understand the pathogenesis of GO. Gingival mucosa showed a decrease of thickness with a lower number of fibroblasts, with reduction of fibrosis areas and decrease of inflammatory infiltrate, and a significant reduction of TGF- 2 expression in roxithromycin treated rats in comparison with animals from the control groups. The present data suggest that the downregulation of TGF- 2 expression may be an important mechanism of action by which roxithromycin inhibits GO.