Positive correlation between blood cyclosporin A level and severity of gingival overgrowth in rats

Cyclosporin a is a drug used to control rejection of organ transplantation and autoimmune diseases; however, it has also been implicated in gingival overgrowth. The present study investigates the relationship between severity of gingival overgrowth and blood cyclosporin A (CsA) levels in Fischer rats treated orally with CsA. Thirty-six 15-day-old male rats were divided into six experimental groups and given powdered rat chow containing 0, 50, 100, 200, 300, and 400 micrograms CsA/g diet ad libitum for 40 days. At the end of the 40-day treatment period, whole blood samples were collected from each rat for assessment of CsA levels. The rats were then sacrificed and the gingival sulcus depth (pseudopocket) around mandibular molars measured to estimate gingival overgrowth. The blood levels of CsA in rats increased with increasing amounts of CsA provided in their food. A 100% incidence in gingival overgrowth was induced in all the rats treated orally with CsA. The overgrowth was more severe in buccal than in lingual gingiva. A significantly positive correlation was found between gingival sulcus depth and the blood CsA level (rs = 0.914, P < 0.0001; Spearman's correlation coefficient by rank). On histological examination, the overgrown gingiva consisted of a thickened epithelial layer and an accumulation of subepithelial fibrous connective tissue components without marked distortion of their proportion.