Effect of cyclosporin A on apoptosis and expression of p53 and bcl-2 proteins in the gingiva of renal transplant patients.
BACKGROUND
Gingival overgrowth (GO) is a common side effect of cyclosporin A (CsA) therapy, but the exact mechanism for this is unknown. Apoptosis plays an important role in the maintenance of tissue homeostasis and mediators of this process may be involved in the pathogenesis of drug-induced GO. This study compared p53 expression, bcl-2 expression, and apoptosis in gingival samples from CsA-treated renal transplant recipients to findings in controls with gingivitis.


METHODS
Twenty-two kidney recipients with CsA-induced GO and 15 systemically healthy subjects with gingivitis were included in the study. The 15 systemically and periodontally healthy volunteer control group were immunohistochemically analyzed for grades of p53 and bcl-2 expression, and were processed using terminal TdT-mediated dUTP-biotin nick-end labeling (TUNEL) technique to identify and grade levels of apoptosis.


RESULTS
There were no differences between the CsA group and the control group with respect to grades of p53 and bcl-2 expression (P >0.05 for both). However, the CsA group showed a lower apoptosis grade than the control group (P <0.05). None of the clinical parameters was significantly correlated with any of the immunohistochemical findings for p53 or bcl-2 (P >0.05 for all). Similarly, grade of apoptosis was not correlated with any of the clinical parameters (P >0.05). There was a significant positive correlation between serum CsA level and level of bcl-2 expression, but serum CsA was not significantly correlated with level of apoptosis or level of p53 expression.


CONCLUSIONS
The results indicate that the pathogenesis of CsA-induced GO might involve inhibition of apoptosis, and overexpression of bcl-2 in the setting of high serum CsA.
Bulut
Sule
S
University of Başkent, Faculty of Dentisty, Department of Periodontology, Ankara, Turkey. suleb@baskent.edu.tr
Ozdemir
B Handan
BH
Alaaddinoĝlu
Emine Elif
EE
Oduncuoĝlu
Füsun Bahar
FB
Bulut
Omer Engin
OE
Demirhan
Beyhan
B
D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism; D005885:Gingival Hyperplasia / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D016572:Cyclosporine