The efficacy and prophylactic characteristics of omega-3 fatty acids in experimental gingivitis in rats

Document Type : Original Article


1 Dental Research Center, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Periodontology, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Histology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran


Objective(s):Gingivitis is an inflammatory disease that affects tooth-supporting tissues and is caused by a microbe-immune response. The aim of this study was to evaluate the effects of omega-3 fatty acids on immune system regulation and the prevention and treatment of gingivitis using an animal model.
Materials and Methods: Gingival inflammation was induced by lipopolysaccharide (LPS) injection. Forty adult male rats were divided into four equal groups: 1. Negative control group (sterile saline was injected into gingival tissue followed by oral gavage with saline); 2. Positive control group (LPS injection was followed by oral gavage with saline); 3. Treatment group (LPS injection was followed by oral gavage with omega-3); 4. Prophylactic group (oral gavage with omega-3 was followed by LPS injection). After 24 days, the rats were sacrificed and histological tissue samples were randomly evaluated for the inflammatory tissue changes. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were measured by ELISA.
Results: The levels of IL-1β and TNF-α in the prophylactic group and the level of TNF-α in the treatment group were significantly lower than those in the positive control group (P<0.05). The severity of inflammation was normal, slight, moderate, and severe in the negative control group, prophylactic group, treatment group, and positive control group, respectively. ANOVA was used for the statistical analyses, with P<0.05 regarded as significant.
Conclusion: Prior consumption of omega-3 fatty acids is effective in reducing inflammation in induced rat gingivitis, resulting in a decreased level of biomarkers and fewer destructive effects.


1. Kantarci A, Hasturk H, Van Dyke TE. Host-mediated resolution of inflammation in periodontal diseases. Periodontol 2000 2006; 40:144-163.
2. Noguchi K, Ishikawa I. The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease. Periodontol 2000 2007; 43:85-101.
3. DeFilippis AP, Sperling LS. Understanding omega-3's. Am Heart J 2006; 151:564-570.
4. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002; 21:495-505.
5. Harbige LS. Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease. Proc Nutr Soc 2008; 57:555-562.
6. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator. Am J Clin Nutr 2000; 71:343S-348S.
7. Engler MM, Engler MB. Omega-3 Fatty Acids: Role in Cardiovascular Health and Disease. J Cardiovasc Nurs 2006; 21:17-24.
8. Gil A. Polyunsaturated fatty acids and inflammatory diseases. Biomed Pharmacother 2002; 56:388-396.
9. Riediger ND, Othman RA, Suh M, Moghadasian MH. A systemic review of the roles of n-3 fatty acids in health and disease. J Am Diet Assoc 2009; 109:668-679.
10. Rosenstein ED, Kushner LJ, Kramer N, Kazandjian G. Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. Prostaglandins Leukot Essent Fatty Acids 2003; 68:213-218.
11. Campan P, Planchand PO, Duran D. Pilot study on n-3 polyunsaturated fatty acids in the treatment of human experimental gingivitis. J Clin Periodontol 1997; 24:907-913.
12.Naqvi AZ, Buettner C, Phillips RS, Davis RB, Mukamal KJ. n-3 fatty acids and periodontitis in US adults. J Am Diet Assoc 2010; 110:1669-1675.
13. Iwasaki M, Yoshihara A, Moynihan P, Watanabe R, Taylor GW, Miyazaki H. Longitudinal relationship between dietary omega-3 fatty acids and periodontal disease. Nutrition 2010; 26:1-5.
14. Iwasaki M, Taylor GW, Moynihan P, Yoshihara A, Muramatsu K, Watanabe R, et al. Dietary ratio of n-6 to n-3 polyunsaturated fatty acids and periodontal disease in community-based older Japanese: A 3-year follow-up study Prostaglandins. Prostaglandins Leukot Essent Fatty Acids 2011; 85:107-112.
15. Hamazaki K, Itomura M, Sawazaki S, Hamazaki T. Fish oil reduces tooth loss mainly through its anti-inflammatory effects? Med Hypotheses 2006; 67:868-8670.
 16. Vardar S, Buduneli E, Türkoğlu O, Berdeli AH, Baylas H, Başkesen A, et al. Therapeutic versus prophylactic plus therapeutic administration of omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2004; 75:1640-1646.
17. Vardar S, Buduneli E, Baylas H, Berdeli AH, Buduneli N, Atilla G. Individual and combined effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2005; 76:99-106.
18. Vardar S, Buduneli N, Buduneli E, Kardeşler L, Baylas H, Atilla G, et al. Dietary supplementation of omega-3 fatty acid and circulating levels of interleukin-1,osteocalcin, and C-reactive protein in rats. J Periodontol 2006; 77:814-820.
19. Kesavalu L, Bakthavatchalu V, Rahman MM, Su J, Raghu B, Dawson D, et al. Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol 2007; 22:232-239.
20. Eberhard J, Heilmann F, Açil Y, Albers HK, Jepsen S. Local application of n-3 or n-6 polyunsaturated fatty acids in the treatment of human experimental gingivitis. J Clin Periodontol 2002; 29:364-369.
21. Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, Serhan CN, et al. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 2007; 179:7021-7029.
22. Dumitrescu AL, Abd-El-Aleem S, Morales-Aza B, Donaldson LF. A model of periodontitis in the rat:effect of lipopolysaccharide on bone resorption, osteoclast activity, and local peptidergic innervation. J Clin Periodontol 2004; 31:596-603.
23. Llavaneras A, Ramamurthy NS, Heikkilä P, Teronen O, Salo T, Rifkin BR, et al. A combination of a Araghizadeh et al Omega-3 fatty acids and rat gingivitis Iran J Basic Med Sci, Vol. 17, No. 2, Feb 2014 91  chemically modified doxycycline and a bisphosphonate synergistically inhibits endotoxin-induced periodontal breakdown in rats. J Periodontol 2001; 72:1069-1077.
24. Kitano S, Irimura K, Sasaki T, Abe N, Baba A, Miyake Y, et al. Suppression of gingival inflammation induced by Porphyromonas gingivalis in rats by leupeptin. J Pharmacol 2001; 85:84-91.
25. Cicek Y, Ozmen I, Canakci V, Dilsiz A, Sahin F. Content and composition of fatty acids in normal and inflamed gingival tissues. Prostaglandins Leukot Essent Fatty Acids 2005; 72:147–151.
26. Bendyk A, Marino V, Zilm P, Howe P, Bartold P. Effect of dietary omega-3 polyunsaturated fatty acids on experimental periodontitis in the mouse. J Periodontal Res 2009; 44:211-216.
27. Iwami-Morimoto Y, Yamaguchi K, Tanne K. Influence of dietary n-3 polyunsaturated fatty acid on experimental tooth movement in rats. Angle Orthod 1999; 69:365-371.