The Relationship between Proliferating Cell Nuclear Antigen Expression and Histomorphometrical Alterations in Cyclosporin A-Induced Gingival Overgrowth in Rats

Abstract

The aim of this study was to investigate the relationship between Proliferating Cell Nuclear Antigen (PCNA) expression and histomorphometrical alterations in cyclosporin A (CsA)-induced gingival overgrowth with or without microbial dental plaque accumulation. Forty male Wistar rats were equally divided into 4 groups; Group I (control); Group II (CsA); Group III (ligature); Group IV (ligature and CsA). After 8 weeks of experimental period, rats were subsequently decapitated and mandibular molars were dissected. Gingival overgrowth was determined by measuring depth of the gingival sulcus, then the mandible were decalcified and serial sections were obtained for histomorphometric and immunohistochemical analysis. Histomorphometric analysis included the measurement of epithelial thickness; immunohistochemical analysis included the assessment of PCNA expression in the oral and sulcular epithelium of buccal and lingual gingiva. Epithelial thickness and PCNA expression were significantly increased in buccal oral epithelium of Group II (p < 0.05) and in all regions in Group IV (p < 0.05) compared to control group. Also gingival overgrowth was more prominent in Group IV in comparison to Group II. These results indicate that CsA-induced gingival alterations are closely associated with increased epithelial proliferative activity, and dental plaque accumulation seems not to be an essential but to be an aggrevating factor for the progression of the lesion.

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

“…Recent studies about proliferation and apoptosis markers in different forms of drug‐induced gingival overgrowth have conflicting results. The expression of proliferation cell nuclear antigen, one of the most popular proliferation markers, was found to be increased in drug‐induced gingival overgrowth 29,52 . More recently, an increase in mitotic activity as measured by the expression of Ki67 and cyclin‐B1 proliferation markers was found in drug‐induced gingival overgrowth 14,53 .…”

“…The expression of proliferation cell nuclear antigen, one of the most popular proliferation markers, was found to be increased in drug-induced gingival overgrowth. 29,52 More recently, an increase in mitotic activity as measured by the expression of Ki67 and cyclin-B1 proliferation markers was found in drug-induced gingival overgrowth. 14,53 On the other hand, Shimizu et al 43 reported that epithelial hyperplasia in nifedipine-induced gingival overgrowth is induced not by an increase in proliferation but by the prolongation of cell life through inhibition of apoptosis.…”

The Effect of Cyclosporin A on Alveolar Bone in Rats Subjected to Experimental Periodontal Disease

“…This model is characterized by accumulation of dental plaque and increased infiltration of inflammatory cells that lead to a degradation of periodontal connective tissue and alveolar bone (Keles et al, 2005). In recent years, the effects of CsA therapy on soft tissues of the periodontium have been extensively investigated in vitro (Bartold 1989;Schincaglia et al, 1992) and in vivo (Seymour et al, 1987;Somacarrera et al, 1994;Cetinkaya et al, 2006aCetinkaya et al, , 2006b. It has been reported that 10 mg/kg daily doses of the drug 720 CETINKAYA ET AL TOXICOLOGIC PATHOLOGY provide plasma peak and trough levels of 1000 and 750 ng/ml (Wassef et al, 1985) and blood levels of CsA between 100-400 ng/ml are sufficient to promote immunosupression in animals (rats, dogs, and monkeys) as well as in humans (Fischer and Klinge, 1994).…”

Spontaneous Gingivitis Related to Hair Penetration in Rats

“…Ca-channel antagonists and Cyclosporine A are known to induce gingival overgrowth in laboratory animals 3 , 4 . Lenz et al 5 reported a dose-related increase in oral squamous carcinoma in a 2-year rat carcinogenicity study with a novel calcium channel antagonist that was not a direct tumorigenic effect of the drug but was attributed to severe periodontal disease due to diet and the class-related gingival overgrowth.…”