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VOLUME 20 , ISSUE 4 ( April, 2019 ) > List of Articles

ORIGINAL RESEARCH

Morphological Comparison of the Changes in the Gingiva of Albino Wistar Rats on Administering Tacrolimus and Sirolimus Separately: An Experimental Study

Karthika J, Rajeev Chandran K

Keywords : Gingival enlargement, Sirolimus, Tacrolimus

Citation Information : J K, K RC. Morphological Comparison of the Changes in the Gingiva of Albino Wistar Rats on Administering Tacrolimus and Sirolimus Separately: An Experimental Study. J Contemp Dent Pract 2019; 20 (4):417-423.

DOI: 10.5005/jp-journals-10024-2532

License: CC BY-NC 4.0

Published Online: 01-04-2019

Copyright Statement:  Copyright © 2019; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

Aim: To morphologically evaluate the effects and compare the magnitude of enlargement in the gingiva of male albino wistar rats, on the administration of tacrolimus and sirolimus. Materials and methods: The experiment was performed on 6-week-old, male Albino Wistar rats, weighing 150–220 g. The animals were housed in pairs, in plastic bottomed cages, with husk as a bedding; in well ventilated rooms subjected to normal atmospheric conditions at 21°C and the same regimen of lighting (12 hours of light/ dark cycle) at the central animal house and fed with a standard pellet diet and water ad libitum. The rats were divided into three groups with 10 rats each and administered 1.5 mg/kg tacrolimus, 2 mg/kg sirolimus and normal saline, respectively for 12 weeks. An impression was made of the rat mandibular incisal region at the end of every third week in polysiloxane impression material, using prefabricated impression trays. The vertical height, buccolingual width and mesiodistal width of the inter-dental papilla and the keratinized gingiva were measured on the study cast using a digital caliper. Statistical analysis was then carried out, and simultaneous comparisons, between the group and within the group were made by using the analysis of variance (ANOVA) repeated measures test. Results: The administration of both tacrolimus and sirolimus resulted in the enlargement of the gingiva, of the albino wistar rats in both the test groups (p <0.001). However, rats administered tacrolimus, showed a greater percentage increase in the gingival dimensions, compared to the sirolimus administered group and the control group, in all the measured dimensions, i.e., vertical height, mesiodistal width and buccolingual width at the end of every third week, in comparison to the baseline (p <0.001). Conclusion: Both drugs, tacrolimus and sirolimus, induced gingival enlargement in the male albino wistar rats. However, the tacrolimus administered group showed a two-fold greater increase in the gingival dimensions compared to the sirolimus administered group. Clinical significance: This study evaluates the effects of tacrolimus and sirolimus on the gingiva of albino wistar rats. Both the drugs are prime members of the immunosuppressive therapy given post-transplantation. Cyclosporine is substituted with tacrolimus to reduce the incidence and intensity of gingival enlargement in such subjects, even though both belong to the same class of drugs, namely calcineurin inhibitors. This study demonstrates that tacrolimus induces gingival enlargement whereas sirolimus does not. There is insufficient literature regarding the effects of sirolimus on gingival tissues. As per the results of this study, Sirolimus may be considered as a better substitute for cyclosporine, than tacrolimus, from a periodontal standpoint.


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  1. Andrews PA. Recent developments in Renal transplantation. BMJ 2002;324:530-534.
  2. Pillai AA, Levitsky J. Immuno update. World J Gastroenterol 2009; 15(34):4225-4233.
  3. Martin L, Michele S, Kellermann G, et al. Cyclosporin A induced gingival overgrowth is not associated with myofibroblast transdifferentiation. Braz Oral Res 2010;24(2):182-188.
  4. Sollecito TP. Transplantation medicine. Burkitts Oral Medicine Chapter 19:503-520.
  5. O'Donnell M, Parmenter KL. Transplant medications. Crit Care Nurs Clin North Am 1996; 8: 253-271.
  6. Braun F, Lorf T, Ringe B. Update of current immunosuppressive drugs used in clinical organ transplantation. Transpl Int 1998;11:77-81.
  7. Zimmerman MA, Trotter JF, Wachs M, et al. Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Liver Transpl 2008;14:633-638.
  8. Kaig, Kelly D, Shaw L. Investigation of the effect of FK506 (tacrolimus) and cyclosporin on gingival overgrowth following paediatric liver transplantation. Int J Paediatr Dent 2002; 12:398-403.
  9. Nassar CA, Nassar PO, Andia DC, et al. The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats, a morphological evaluation. Oral Dis 2008;14:67-72.
  10. Ellis JS, Seymour RA, Taylor JJ, et al. Prevalence of gingival overgrowth in transplant patients immunosuppressed with tacrolimus. J Clin Periodontol 2004;31:126-131.
  11. Sekiguchi RT, Paixa CG, Saraiva L, et al. Incidence of tacrolimusinduced gingival overgrowth in the absence of calcium channel blockers, a short-term study. J Clin Periodontol 2007;34:545-550.
  12. Thervet E. Sirolimus therapy following early cyclosporin withdrawal in transplant patients: Mechanism of action and clinical results. Int J of Nanomed 2006;1(3):269-281.
  13. Cota LO, Oliveira AP, Costa JE, et al. Gingival status of Brazilian renal transplant recipients under sirolimus-based regimens. J Periodontol 2008;79(11):2060-2068.
  14. Johnsson C, Gerdin B, Tufveson G. Effects of commonly used immunosuppressants on graft-derived fibroblasts. Clin Exp Immunol 2004;136:405-412.
  15. Pierre E. Wallema CQ, Reding R. FK506 (Tacrolimus), A Novel Immunosuppressant in Organ Transplantation, Clinical, Biomedical and Analytical Aspects. Clin Chem 1993;39(11):2219-2228.
  16. Fairbanks KD, Eustace JA, Fine D, et al. Renal Function Improves in Liver Transplant Recipients When Switched From a Calcineurin Inhibitor to Sirolimus. Liver Transpl 2003;9:1079-1085.
  17. Bumbea V, Kamar N, Ribes D, et al. Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus. Nephrol Dial Transplant 2005;20: 2517-2523.
  18. De Beek DV, Kremers WK, Kushwaha SS, et al. No Major Neurologic Complications With Sirolimus Use in Heart Transplant Recipients. Mayo Clin Proc 2009;84(4): 330-332.
  19. Hassell TM, Hefti AF. Drug-Induced Gingival Overgrowth: Old Problem, New Problem, CROBM 1991;2(1):103-137.
  20. Bader G, Lejeune S, Messner M. Reduction of cyclosporin induced gingival overgrowth following a change to tacrolimus - A case history involving a liver transplant patient. J Periodontology 1998;69(6):729-732.
  21. Hernandez G, Arriba L, Lucas M, et al. Reduction of severe gingival overgrowth in a kidney transplant patient by replacing cyclosporin A with tacrolimus. J Periodontol 2000;71(10):1630-1636.
  22. James JA, Boomer S, Maxwell AP, et al. Reduction in gingival overgrowth associated with conversion from cyclosporin A to tacrolimus. J Clin Periodontol 2000;27(2):144-148.
  23. James JA, Jamal S, Hull PS, et al. Tacrolimus is not associated with gingival overgrowth in renal transplant patients. J Clin Periodontol 2001;28(9):848-852.
  24. Chabria D, Weintraub RG, Kilpatrick NM. Mechanisms and management of gingival ov ergrowth in paediatric transplant recipient- a review. Int J Paediatric Dentistry 2003;13(4):220-229.
  25. Gagliano N, Moscheni C, Dellavia C, et al. Immunosuppression and gingival overgrowth: gene and protein expression profiles of collagen turnover in FK506-treated human gingival fibroblasts. J Clin Periodontol Feb; 32(2): 167-173.
  26. Prabhu A, Mehta DS. A Morphological Comparison of Gingival Changes Influenced by Cyclosporin and Tacrolimus in Rats: An Experimental Study. J Periodontol 2006;77:265-270.
  27. Oliveira CF, Ferreira SD, Lages EJ, et al. Demographic, pharmacologic, and periodontal variables for gingival overgrowth in subjects medicated with cyclosporin in the absence of calcium channel blockers. J Periodontol 2007;78(2):254-261.
  28. Cezario ES, Cota LO, Ferreira SD, et al. Gingival overgrowth in renal transplant subjects medicated with tacrolimus in the absence of calcium channel blockers. Transplantation 2008;85(2): 232-236.
  29. Cota LOM, Aquino DR, Francoc GCN, et al. Gingival overgrowth in subjects under immunosuppressive regimens based on cyclosporin, tacrolimus, or sirolimus. J Clin Periodontol 2010;37(10):894-902.
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