Citation Information :
Eftekharian S, Seifi S, Satari FD, Moghaddamnia AA, Feizi F, Kazemi S, Gholinia H. Curcumin Effect on the Prevention of Gingival Overgrowth Following Phenytoin Consumption in Rats: A Clinicohistological and Immunohistochemical Study. J Contemp Dent Pract 2019; 20 (10):1146-1150.
Aim: At the moment there is no clear evidence with clinico-histological and immunohistochemical studies in animals to show the curcumin effect on the gingival overgrowth following phenytoin consumption. The purpose of the present study was to identify this subject.
Materials and methods: In this experimental study, 50 adult male Wistar rats were divided into three groups. The rats in groups I and II received 100 mg/kg of phenytoin per day. Group II also received 20 mg/kg intraperitoneal curcumin per day. The control group received the curcumin vehicle only. Gingival clinical dimensions were measured at the beginning and end of the study. The rats were then sacrificed, biopsy of gingiva was prepared, and the samples were stained with hematoxylin–eosin. Morphometry was performed to evaluate the degree of inflammation, epithelial thickness, number, and cross-sectional area of the blood vessels. Immunohistochemical staining was performed using Ki67 and α-SMA.
Results: Compared to the control group, Phenytoin in group I increased gingival volume. There was significance difference in group II with group I and control after intervention in the clinical view (p = 0.002). The difference in the number of blood vessels between groups I and II was statistically significant (p = 0.001). Significant differences were observed in blood vessel cross-sectional area (p = 0.001), epithelial thickness (p = 0.002), Ki67, and α-SMA expression between groups I and II (p = 0.001).
Conclusion: In rats, curcumin seems to exerts its effects in preventing an increase in gingival volume caused by Phenytoin through decreasing the inflammatory infiltration, decreasing the number of blood vessels and increasing their cross-sectional area, decreasing the thickness of the epithelium, and decreasing the expression of Ki67 and α-SMA.
Clinical significance: It is suggested that curcumin may be effective in treatment of gingival enlargement following Phenytoin consumption in future. Larger sample size and clinical trials study are recommended.
Black S, Palamakumbura A, et al. Tissue-specific Mechanisms for CCN2/CTGF Persistence in Fibrotic Gingiva: interactions between cAMP and MAPK signaling pathways, and prostaglandin E2-EP3 receptor mediated activation of the c-JUN N-terminal kinase. J Biol Chem 2007 May;282(21):15416–15429. DOI: 10.1074/jbc. M610432200.
Chen Y, Yang W, et al. Curcumin Inhibits Thrombin-Stimulated Connective Tissue Growth Factor (CTGF/CCN2) Production Through c-Jun NH2-Terminal Kinase Suppression in Human Gingival Fibroblasts. J Periodontol 2012 Dec;83(12):1546–1553. DOI: 10.1902/jop.2012.110641.
Yang W-H, Kuo M-P, et al. Curcumin Inhibits TGFβ1-induced CCN2 via Src, JNK, and Smad3 in Gingiva. J Dent Res 2013 Jul;92(7):629–634. DOI: 10.1177/0022034513488139.
Seifi S, Shafaei SH, et al. Myofibroblast stromal presence and distribution in squamous epithelial carcinoma, oral dysplasia and hyperkeratosis. Asian Pac J Cancer Prev 2010 Dec;11(2): 359–364.
Salva Guegel GA, Goncalres Ramos EA, et al. Expression of ki 67, p53 and p53 protein in keratocyctic odontogenic tumors: an immunohistochemical study. J Mol Histol 2008 Jun;39(3):311–316. DOI: 10.1007/s10735-008-9167-0.
Tusgino T, Seshimo I, et al. Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res 2007 Apr;13(7): 2082–2090. DOI: 10.1158/1078-0432.CCR-06-2191.
Okuneif P, Xu J, et al. Curcumin Protects Against Radiation-Induced Acute And Chronic Cutaneous Toxicity in Mice And Decreases mRNA Expression of Inflammatory and Fibrogenic Cytokins. Int J Radiat Oncol Biol Phys 2006 Jul;65(3):890–898. DOI: 10.1016/j.ijrobp.2006.03.025.
Nashikava S, Nagata T, et al. Pathogenesis of drug-induced gingival overgrowth. A review of studies in the rat model. J Periodontol 1996 May;67(5):463–471. DOI: 10.1902/jop.1918.104.22.1683.
Rokn AR, Khodadostan MA, et al. Bone formation with two types of grafting materials: a histologic and histomorphometric study. Open Dent J 2011 Jul;5:96–104. DOI: 10.2174/1874210601105010096.
Bulut S, Uslu H, et al. Analysis of proliferation activity in oral gingival epithelium in immunosuppressive medication induced gingival overgrowth. Head Face Med 2006 May;2:13. DOI: 10.1186/1746-160X-2-13.
Seifi S, Shafaie S, et al. Microvessel density in follicular cysts, keratocystic odontogenic tumours and ameloblastomas. Asian Pac J Cancer Prev 2011;12(2):351–356.
Troijilo J, Irasema Y. Renoprotective of the effect of curcumine. Epilepsy Res 2011 Jul;26(1):207–218.
Morgana R, Sabrina G, et al. Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate Immunity 2012 Feb;18(1):155–163. DOI: 10.1177/1753425910392935.
Bisht S, Muzuma M, et al. Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc™) blocks tumor growth and metastases in preclinical models of pancreatic cancer. Mol Cancer Ther 2010 Aug;9(8):2255–2264. DOI: 10.1158/1535-7163.MCT-10-0172.
Sume SS, Kantarci A, et al. Epithelial to mesenchymal transition in gingival overgrowth. Am J Pathol 2010;177:208–218. DOI: 10.2353/ajpath.2010.090952.
John KC, Chan MD. The wonderful colors of the hematoxylin-eosin stain in diagnostic surgical pathology. Int J Surg Pathol 2014;22(1): 12–32. DOI: 10.1177/1066896913517939.
Tamamori Y, Tamura Y, et al. Establishment of Rat Model of Drug-Induced Gingival Overgrowth Induced by Continuous Administration of Phenytoin. J Pharmacol Sci 2005 Jul;98:290–297. DOI: 10.1254/jphs.FPJ04028X.