THE EFFECTS OF ALPHA-TOCOPHEROL ON SERUM IL-1, IL-4 AND IL-6 LEVELS OF RATS WITH EXPERIMENTAL PERIODONTITIS AND TYPE I DIABETES

Öz

Background: Epidemiologic and clinical studies have indicated that periodontal disease may affect diabetes. On the other hand periodontitis is one of the complications of diabetes. The goal of this study was to investigate the effects of  -tocopherol administration on serum cytokine concentrations in rats with experimental periodontitis with/without streptozotocin (STZ)-induced diabetes. Methods: Totally fourty male Sprague Dawley rats were anesthetized, and 3/0 silk sutures were placed at the subgingival level of the mandibular right first molars. These animals were divided into two groups: Healty group (Group I) and diabetic group by single injection of 50mg/kg STZ(Group II). These groups divided into two subgroups; twenty rats were saline group (Group IA, Group IIA) and other twenty rats (Group IB, Group IIB) were  -tocopherol (40mg/ kg/day) group. The animals were sacrificed 21 days after ligature placement. At these time period, blood samples were taken in order to measure the concentrations(pg/ml) of serum IL-1 , IL-4 and IL-6 levels by using commercial ELISA kits. Statistical comparisons were performed by using two-way analysis of variance with significance set at p<0.05. Results: Analysis of datas demonstrated that, no statistically significant differences were found in serum IL-1  , IL-4 ve IL-6 concentrations between the study groups (p 0.05). Conclusion: These results indicated that  tocopherol was not effected the serum cytokine concentrations of rats with experimental periodontitis with/without STZ-induced diabetes.

Anahtar Kelimeler

• Cytokine
•  -tocopherol
• diabetes
• experimental periodontitis.

TİP I DİYABET OLUŞTURULMUŞ DENEYSEL PERİODONTİTİSLİ SIÇANLARDA ALFA-TOKOFEROL’UN SERUM IL-1, IL-4 VE IL-6 DÜZEYLERİ ÜZERİNE ETKİLERİ

Öz

Amaç: Epidemiyolojik ve klinik çalışmalar periodontal hastalığın diyabeti etkileyebileceğini göstermiştir, diğer taraftan periodontitis diyabetin komplikasyonlarından birisidir. Bu çalışmanın hedefi, deneysel periodontitis ve streptozotosin (STZ) ile diyabet oluşturulan/ oluşturulmayan sıçanlarda  -tokoferol uygulamasının serum sitokin düzeyleri üzerine etkilerini araştırmaktır. Gereç ve Yöntemler: Toplam kırk adet erkek Sprague Dawley sıçana anestezi uygulandı ve mandibular sağ birinci molar dişlere subgingival olarak 3/0 ipek sütur bağlandı. Bu hayvanlar, sağlıklı grup (Grup I) ve tek seferde 50mg/kg STZ enjekte edilen diyabetik grup (Grup II) olmak üzere iki gruba ayrıldı. Bu gruplarda serum fizyolojik (Grup IA, Grup IIA) ve  tokoferol (40mg/kg/gün) enjekte edilen alt gruplara (Grup IB, Grup IIB) ayrıldı. Ligatür bağlandıktan 21 gün sonra sıçanlar kurban edildi. Aynı zaman aralığında serum IL-1 , IL-4 ve IL-6 konsantrasyonlarının (pg/ml) ticari ELISA kitleri kullanılarak ölçülebilmesi için kan örnekleri alındı. İstatistiksel kıyaslamalar için iki-yönlü varyans analizi kullanıldı p<0.05 anlamlılık düzeyi kabul edildi. Bulgular: Verilerin analizi sonunda, gruplar arasında serum IL-1 , IL-4 ve IL-6 konsantrasyonları istatistiksel olarak farklı bulunmadı (p>0.05). Sonuçlar: Elde edilen sonuçlara göre  -tokoferol’ün deneysel periodontitisli, STZ ile diyabet oluşturulmuş/oluşturulmamış sıçanlarda serum IL-1 , IL-4 ve IL-6 konsantrasyonlarını değiştirmediği belirlenmiştir.

Anahtar Kelimeler

• Sitokin
• -tokofero
• diyabet
• deneysel periodontitis.

Kaynakça

1. Flemmig TF. Periodontitis. Ann Periodontol 1999; 4: 32- 7.
2. Mariotti A. Dental plaque-induced gingival diseases. Ann Periodontol 1999; 4: 7-17.
3. Carranza FA, Newman MG, Takei HH, Klokkevold PR. Etiology of periodontal disease. In: Clinical Periodontology. Ed. John Dolan. 10th ed. Saunders. Missouri, p: 134-282, 2007.
4. Al Shamsi M, Amin A, Adeghate E. Effect of vitamin C on liver and kidney functions in normal and diabetic rats. Annals New York Academy of Sciences 2006; 1084: 371-90.
5. Seymour RA, Preshaw PM, Thomason JM, Ellis JS, Steele JG: Cardiovascular diseases and periodontology. J Clin Periodontol 2003; 30: 279
6. Heitz-Mayfield LJA. Disease progressison: identification of high-risk groups and individuals for periodontitis. J Clin Periodontol 2005; 32: 196-209. Linden G, Patterson C, Evans A, Kee F. Obesity and periodontitis in 60-70-year-old men. J Clin Periodontol 2007; 34: 461-6.
7. Khader YS, Bawadi HA, Haroun TF, Alomari M, Tayyem RF. The association between periodontal desease and abesity among adult in Jordan. J Clin Periodontol 2009; 36: 18-24.
8. Tsai C, Hayes C, Taylor GW. Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community Dent Oral Epidemiol 2002; 30: 182-92.

9. Campus G, Salem A, Uzzau S, Baldoni E, Tonolo G. Diabetes and Periodontal disease: A case-control study. J Periodontol 2005; 76: 418-425.
10. Benguigui C, Bongard V, Ruidavets J-B, Chamontin B, Sixou M, FerriEres J, Amar J. Metabolic syndrome, insulin resistance and periodontitis: a cross- sectional study in a middle-aged French population. J Clin Periodontol 2010; 37: 601-8.
11. Lo Y-J, Liu C-M, Wong M-Y, Hou L-T, Chang W-K. Interleukin 1β-secreting cells in inflamed gingival tissue of adult periodontitis patients. Cytokine 1999; 11: 626-33.
12. Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL33 families of cytokines. Immunological Reviews. 2008; 223: 20-38.
13. Stashenko P, Fujiyoshi P, Obernesser MS, Prostak L, Haffajee AD, Socransky SS: Levels of interleukin lβ in tissue from sites of active periodontal disease. J Clin Periodontol 1991a; 18: 548-54.
14. Hirose M, Ishihara K, Saito A, Nakagawa T, Yamada S, Okuda K. Expression of ctokines and inducible nitric oxide synthase in inflamed gingival tissue. J Periodontol 2001; 72: 590-7.
15. Ejeil A-L, Gaultier F, Igondjo-Tchen S, Seni K, Pellat B, Gordeau G, Gogly B. Are cytokines linked to collagen breakdown during periodontal disease progression. J Periodontol 2003;74:196-201.
16. Dennison DK, Van Dyke TE. The acute inflammatory response and the role of phagocytic cells in periodontal health and disease. Periodontology 2000 1997; 14: 54-78.
17. Gemmell E, Marshall RI, Seymour GJ. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontology 2000 1997; 14: 112-43.
18. Górska R, Gregorek H, Kowalski J, LaskusPerendyk A, Syczewska M, Madaliński K.Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis. J Clin Periodontol 2003; 30: 1046
19. Bastos MF, Lima JA, Vieira PM, Mestnik MJ, Faveri M, Duarte PM. TNF-α and IL-4 levels in generalized aggressive periodontitis subjects. Oral Diseases 2009; 15: 82-7.
20. Buhlin K, Hultin M, Norderyd O, Persson L, Pockley AG, Klinge B, Gustafsson A. Risk factors for atherosclerosis in cases with severe periodontitis. J Clin Periodontol 2009; 36: 541-9.
21. Thomson A. The cytokine handbook. Third edition, California, Academic Press, 1998: 35-227.
22. Hedayat M, Mahmoudi MJ, Rose NR, Rezaei N. Proinflammatory cytokines in heart failure: doubleedged swords. Heart Fail Rev. 2010; 1007: 1-20.
23. Franchimont N, Rydziel S, Canalis E. Interleukin 6 is autoregulated by transcriptional mechanisms in cultures of rat osteoblastic cells. J Clin Invest. 1997; 100: 1797-803.
24. Schwartz Z, Goultschin J, Dean DD, Boyan BD. Mechanisms of alveolar bone destruction in periodontitis. Periodontology 2000. 1997;14: 581
25. Naka T, Nishimoto N, Kishimoto T. The paradigm of IL-6: from basic science to medicine. Arthritis Res 2002; 4: 233-42.
26. Di Paola R, Mazzon E, Zito D, Maiere D, Britti D, Genovese T, Cuzzocrea S. Effects of Tempol, a membrane-permeable radical scavenger, in a rodent model periodontitis. J Clin Periodontol 2005; 32: 1062-8.
27. Neiva RF, Al-Shammari K, Nociti Jr FH, Soehren S, Wang H-L. Effects of vitamin-B complex supplementation on periodontal wound healing. J Periodontol 2005; 76: 1084-91.
28. Tomofuji T, Ekuni D, Irie K, Azuma T, Endo Y, Tamaki N, Sanbe T, Murakami J, Yamamoto T, Morita M. Preventive effects of a cocoa-enriched diet on gingival oxidative stress in experimental periodontitis. J Periodontol 2009; 80: 1799-808.
29. Sen CK, Khanna S, Roy S. Tocotrienols: Vitamin E beyond tocopherols. Life Sciences 2006; 78: 2088
30. Bursell S-E, Clermont AC, Aiello LP, Aiello LM, Schlossman DK, Feener EP, Laffel L, King GL. HighDose vitamin E supplementation normalizes retinal blood flow and C reatinine clearance in patients with type 1 diabetes. Diabetes Care 1999; 22: 1245Wan Nazaimoon WM, Khalid BAK. Tocotrienols-rich diet decreases advanced glycosylation endproducts in non-diabetic rats and improves glycemic control in streptozotocin-induced diabetic rats. Malaysian J Pathol 2002; 24: 77-82.
31. Pekiner BD, Evcimen ND, Ulusu NN, Bali M, Karasu Ç. Effects of vitamin E on microsomal Ca 2+ -ATPase activity and calcium levels in streptozotocininduced diabetic rat kidney. Cell Biochem Funct 2003; 21: 177-82.
32. Manning PJ, Sutherland WHF, Walker RJ, Williams SM, Jong SA, Ryalls AR, Berry EA. Effect of highdose vitamin E on insulin resistance and associatted parameters in overweight subject. Diabetes Care 2004; 27: 2166-71.
33. Dinarello CA. Proinflammatory ctokines. Chest. 2000; 118; 503-8.
34. Stashenko P, Jandinski JJ, Fujiyoshi P, Rynar J, Socransky SS. Tissue Levels of Bone Resorptive Cytokines in Periodontal Disease. J Periodontol 1991; 62: 504-9.
35. Dongari-Bagtzoglou Al, Ebersole JL. Increased presence of interleukin-6 (IL-6) and IL-8 secreting fibroblast subpopulations in adult periodontitis. J Periodontol 1998; 69: 899-910.
36. Giannopoulou C, Kamma JJ, Mombelli A. Effect of inflammation, smoking and stress on gingival crevicular fluid cytokine level. J Clin Periodontol 2003; 30:145-53.
37. Loos BG, Craandijk J, Hoek FJ, Paulien ME, van Dillen W, van der Velden U. Elevation of systemic markers related to cardiovascular diseases in the pheriferal blood of periodontitis patients. J Periodontol 2000;71: 1528-34.
38. Borrell LN, Papapanou PN. Analytical epidemiology of periodontitis. J Clin Periodontol 2005; 32: 132
39. King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontol 2008; 79: 1527-34.
40. Choudhary N, Ahlawat RS. Interleukin-6 and CReactive protein in pathogenesis of diabetic nephropathy new evidence linking inflammation, glycemic control, and microalbuminuria. IJKD. 2008; 2: 72-9.
41. Andreozzi F, Laratta E, Procopio C, Hribal MA, Sciacqua A, Perticone M, Miele C, Perticone F, Sesti G. İnterleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. Molecular and Cellular Biology 2007; 27: 2372-83.
42. Engebretson SP, Hey-Hadavi J, Ehrhardt FJ, Hsu D, Celenti RS, Grbic JT, Lamster IB. Gingival crevicular fluid levels of interleukin-1  and glycemic control in patients with chronic periodontitis and type 2 diabetes. J Periodontol 2004; 75: 1203-8.
43. Andersen CCP, Buschard K, Flyvbjerg A, Stoltze K, Holmstrupt P. Periodontitis deteriorates metabolic control in type 2 diabetic Goto- Kakizaki rats. J Periodontol 2006; 77: 350-6.
44. Santos VR, Ribeiro FV, Lima JA, Napimoga MH, Bastos MF, Duarte PM: Cytokine levels in sites of chronic periodontitis of poorly controlled and wellcontrolled type 2 diabetic subjects. J Clin Periodontol 2010; 37: 1049-58.
45. Doxey DL, Cutler CW, Iacopino AM. Diabetes prevents periodontitis-induced increases in gingival platelet derived growth factor-B and interleukin 1Beta in a rat model, J Periodontol 1998, 69, 113-9. Salvi GE, Franco LM, Braun TM, Lee A, Rutger Persson G, Lang NP, Giannobile WV. Proinflammatory biomarkers during experimental gingivitis in patients with type 1 diabetes mellitus: a proof-of-concept study. J Clin Periodontol 2010; 37: 9-16.
46. Andriankaja OM, Barros SP, Moss K, Panagakos FS, DeVizio W, J. Beck J, Offenbacher S. Levels of serum interleukin (IL-6) and gingival crevicular fluid of IL-1  and prostaglandin E2 among nonsmoking subjects with gingivitis and Type 2 diabetes. J Periodontol 2009; 80: 307-16.
47. Correa FOB, Gonçalves D, Figueredo CMS, Gustafsson A, Orrico SRP. The short-term effectiveness of non-surgical treatment in reducing levels of interleukin-1 and proteases in gingival crevicular fluid from patients with type 2 diabetes mellitus and chronic periodontitis. J Periodontol 2008; 79: 2143-50.
48. Shin D-S, Park J-W, Suh J-Y, Lee J-M. The expressions of inflammatory factors and tissue inhibitor of matrix metalloproteinase-2 in human chronic periodontitis with type 2 diabetes mellitus. J Periodontal Implant Sci 2010; 40:33-8.
49. Venza I, Visalli M, Cucinotta M, De Grazia G, Teti D, Venza M. Proinflammatory gene expression at chronic periodontitis and peri-implantitis sites in patients with or without Type 2 diabetes. J Periodontol 2010; 81: 99-108.
50. O’Connell PAA, Taba M Jr, Nomizo A, Freitas MCF, Suaid FA, Uyemura SA, Trevisan GL, Novaes AB Jr, Souza SLS, Palioto DB, Grisi MFM. Effects of Periodontal therapy on glycemic control and inflammatory markers. J Periodontol 2008; 79:774
51. Vega-Lopez S, Kaul N, Devaraj S, Cai RY, German B, Jialal I. Supplementation with  3 polyunsaturated fatty acids and all-rac alphatocopherol alone and in combination failed to exert an anti-inflammatory effect in human volunteers. Metabolism 2004; 53: 236-40.
52. Norazlina M, Lee PL, Lukman HI, Nazrun AS, ImaNirwana S. Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats. Singapore Med J 2007; 48: 195-9.
53. Devaraj S, Leonard S, Traber MG, Jialal I. Gammatocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome. Free Radical Biology & Medicine 2008; 44: 1203-8.
54. Tits LJ, Demacker PN, Graaf J, Hak-Lemmers HL, Stalenhoef AF.  -Tocopherol supplementation decreases production of superoxide and cytokines by leukocytes ex vivo in both normolipidemic and hypertriglyceridemic individuals. Am J Clin Nutr 2000; 71: 458-64.
55. Godbout JP, Berg BM, Kelley KW, Johnson RW.  Tocopherol reduces lipopolysaccharide-induced peroxide radical formation and interleukin-6 secretion in primary murine microglia and in brain. Journal of Neuroimmunology 2004; 149: 101-9.
56. Godbout JP, Berg BM, Krzyszton C, Johnson RW.  -Tocopherol attenuates NF  B activation and proinflammatory cytokine production in brain and improves recovery from lipopolysaccharide-induced sickness behavior. Journal of Neuroimmunology 2005; 169: 97-105.
57. Mol MJTM, de Rijke YB, Demacker PNM, Stalenhoef AFH. Plasma levels of lipid and cholesterol oxidation products and cytokines in diabetes mellitus and cigarette smoking: effects of vitamin E treatment. Atherosclerosis 1997; 129: 169Devaraj S, Jialal I.  -tocopherol decreases interleukin-1  release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler Thromb Vasc Biol 1999; 19: 1125-33.
58. Devaraj S, Jialal I. Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in Type 2 diabetic patients with and without macrovascular complications. The effect of  -tocopherol supplementation. Circulation 2000;102: 191-6.
59. Devaraj S, Jialal I. Alpha tocopherol supplementatıon decreases serum c-reactive proteın and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radical Biology & Medicine 2000; 29: 790-2. Wu JHY, Ward NC, Indrawan AP, Almeida C-A, Hodgson JM, Proudfoot JM, PuddeyIB, Croft KD. Effects of  -tocopherol and mixed tocopherol supplementation on markers of oxidative stres and inflammation in type 2 diabetes. Clinical Chemistry 2007; 53: 511-9. Yazışma Adresi: Uzm. Dr. Mükerrem HATİPOĞLU.
60. Akdeniz Üniversitesi Diş Hekimliği Fakültesi Periodontoloji Anabilim Dalı Kampüs/Antalya. e-posta: [e-mail]