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

Abstract

Background: The aim of this study is to compare gingival changes induced by short-and long-term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug-induced gingival over-growth. Methods: Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8-week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24-week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (V-f), collagen fibers (V-cf), and blood vessels (V-b upsilon). In addition, PTEN expression was analyzed using immunohistochemistry. Results: Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P <0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P <0.001). V-f and Vcf were significantly increased in group 7 compared to group 8 (P <0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P <0.05). Conclusions: Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's