Inhibition of cyclosporin A-induced gingival overgrowth by azithromycin through phagocytosis: An in vivo and in vitro study

BACKGROUND: The objective of the present study was to investigate the effect of cyclosporin A (CsA) and azithromycin (AZI) on collagen metabolism in the gingiva of rats. METHODS: Fifty 6-week-old male Sprague-Dawley (SD) rats (weight 120 to 150 g) were randomly distributed into five groups. All groups received various drugs via gastric feeding for 7 weeks. The first group (Mo group) received mineral oil for 7 weeks as a control; the CsA group received CsA in mineral oil for 7 weeks (dosage 30 mg/kg); the CsA/Mo group received CsA in mineral oil for 6 weeks and mineral oil only for the seventh week; the CsA/AZI group received CsA in mineral oil for 6 weeks and AZI (dosage 10 mg/kg) in mineral oil simultaneously with CsA in the seventh week; and the Mo/AZI group received mineral oil for 6 weeks and AZI in mineral oil for the seventh week. All animals were sacrificed for clinical and histological analyses. Gingival fibroblasts were cultured at the fourth passage, and the amount of collagen was measured. Type I collagen and collagenase mRNA were measured by reverse transcription-polymerase chain reaction. Collagen phagocytosis assay also was performed. RESULTS: Clinically, CsA induced gingival overgrowth in rats, whereas AZI reduced gingival overgrowth. Histological results of the CsA group showed a marked increase of tissue volume compared to the other groups. High collagen amounts were found when gingival overgrowth was induced. However, type I collagen mRNA and collagenase mRNA expressions did not statistically differ among groups. Phagocytosis assay showed that CsA decreased phagocytic activity of gingival fibroblasts, whereas AZI increased the activity. These results suggest that the induction and reduction of CsA-induced gingival overgrowth were closely associated with phagocytic activity. CONCLUSION: Cyclosporin A decreases collagen degradation by lowering phagocytic activity of rat gingival fibroblasts. Azithromycin partially compensates for this lowered phagocytic activity.ope