Objective: This study aimed to investigate the anti-inflammatory effect of two different dosages of caffeic acid phenethyl ester (CAPE) on lipopolysaccharide-induced experimental periodontitis (EP). Material and Methods: Forty Sprague Dawley rats were randomly divided into four groups: control, EP, EP treated with 5 μmol/kg/day of CAPE (EP+CAPE 5), and EP treated with 10 μmol/kg/day of CAPE (EP+CAPE 10). Followed by the EP, CAPE was administered intraperitoneally to the EP+CAPE groups for 28 days. Samples were investigated biochemically using an enzyme-linked immunosorbent assay kit and alveolar bone loss was measured morphometrically. Results: In both of the CAPE groups, the levels of interleukin-1 beta and tumor necrosis factor alpha (TNF-α) in the gingiva were significantly lower than those in the EP group (p<0.001). The decrease in tissue levels of TNF-α was greater in the EP+CAPE 10 group than in the EP+CAPE 5 group in a dose-dependent manner. Serum analysis of the cytokines showed no significant difference between the groups. Conclusion: Within the limits of this study, CAPE showed an anti-inflammatory effect and is claimed to be a novel agent in improving the results of periodontal therapy. CAPE may be valuable as an alternative host modulating agent for the treatment of periodontal disease.
Keywords: Caffeic acid phenethyl ester; periodontal diseases; interleukin-1 beta; tumor necrosis factor-alpha
Amaç: Bu çalışma, 2 farklı dozda kafeik asit fenetil esterin (KAFE) lipopolisakkarit ile indüklenen deneysel periodontitis (DP) üzerindeki antiinflamatuar etkisini araştırmayı amaçlamıştır. Gereç ve Yöntemler: Kırk Sprague Dawley sıçanı rastgele 4 gruba ayrılmıştır: kontrol, DP, 5 μmol/kg/gün KAFE ile tedavi edilen DP (DP+KAFE 5) ve 10 μmol/kg/gün KAFE ile tedavi edilen DP (DP+KAFE 10). DP'yi takiben DP+KAFE gruplarına 28 gün süreyle intraperitoneal olarak KAFE uygulanmıştır. Numuneler, enzim bağlı immünosorbent tahlil kiti kullanılarak biyokimyasal olarak araştırılmış ve alveolar kemik kaybı morfometrik olarak ölçülmüştür. Bulgular: Her iki KAFE grubunda da diş eti interlökin-1 beta ve tümör nekroz faktörü-alfa (TNF-α) seviyeleri DP grubuna göre anlamlı derecede düşük bulunmuştur (p<0,001). TNF-α'nın doku seviyelerindeki düşüş, doza bağlı bir şekilde DP+KAFE 5 grubuna göre DP+KAFE 10 grubunda daha fazla olmuştur. Sitokinlerin serum analizi, gruplar arasında anlamlı bir farklılık göstermemiştir. Sonuç: Bu çalışmanın sınırları dâhilinde, KAFE'nin antiinflamatuar etkisi gösterilmiş ve periodontal tedavinin sonuçlarını arttırmada etkili bir ajan olabileceği ileri sürülmüştür. KAFE, periodontal hastalığın tedavisi için alternatif bir konak modüle edici ajan olarak değerli olabilir.
Anahtar Kelimeler: Kafeik asit fenetil ester; periodontal hastalıklar; interlökin-1 beta; tümör nekroz faktörü-alfa
- Cho MI, Garant PR. Development and general structure of the periodontium. Periodontol 2000. 2000;24:9-27. [Crossref] [PubMed]
- Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol. 2003;74(3):391-401. [Crossref] [PubMed]
- Yavuzyilmaz E, Yamalik N, Bulut S, Ozen S, Ersoy F, Saatçi U. The gingival crevicular fluid interleukin-1 beta and tumour necrosis factor-alpha levels in patients with rapidly progressive periodontitis. Aust Dent J. 1995;40(1):46-9. [Crossref] [PubMed]
- Górska R, Gregorek H, Kowalski J, Laskus-Perendyk 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(12):1046-52. [Crossref] [PubMed]
- Assuma R, Oates T, Cochran D, Amar S, Graves DT. IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol. 1998;160(1):403-9. [PubMed]
- Kirkwood KL, Cirelli JA, Rogers JE, Giannobile WV. Novel host response therapeutic approaches to treat periodontal diseases. Periodontol 2000. 2007;43:294-315. [Crossref] [PubMed] [PMC]
- Caton JG, Ciancio SG, Blieden TM, Bradshaw M, Crout RJ, Hefti AF, et al. Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontol. 2000;71(4):521-32. [Crossref] [PubMed]
- Bjarnason I, Scarpignato C, Holmgren E, Olszewski M, Rainsford KD, Lanas A. Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs. Gastroenterology. 2018;154(3):500-14. [Crossref] [PubMed]
- Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, et al; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22(10):1479-91. [Crossref] [PubMed]
- Slots J, Rams TE. Antibiotics in periodontal therapy: advantages and disadvantages. J Clin Periodontol. 1990;17(7 ( Pt 2)):479-93. [Crossref] [PubMed]
- Preshaw PM. Host modulation therapy with anti-inflammatory agents. Periodontol 2000. 2018;76(1):131-49. [Crossref] [PubMed]
- Palaska I, Papathanasiou E, Theoharides TC. Use of polyphenols in periodontal inflammation. Eur J Pharmacol. 2013;720(1-3):77-83. [Crossref] [PubMed]
- Velazquez C, Navarro M, Acosta A, Angulo A, Dominguez Z, Robles R, et al. Antibacterial and free-radical scavenging activities of Sonoran propolis. J Appl Microbiol. 2007;103(5):1747-56. [Crossref] [PubMed]
- Chen YJ, Shiao MS, Wang SY. The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells. Anticancer Drugs. 2001;12(2):143-9. [Crossref] [PubMed]
- Akyol S, Ozturk G, Ginis Z, Armutcu F, Yigitoglu MR, Akyol O. In vivo and in vitro antineoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives. Nutr Cancer. 2013;65(4):515-26. [Crossref] [PubMed]
- da Cunha FM, Duma D, Assreuy J, Buzzi FC, Niero R, Campos MM, et al. Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties. Free Radic Res. 2004;38(11):1241-53. [Crossref] [PubMed]
- Orban Z, Mitsiades N, Burke TR Jr, Tsokos M, Chrousos GP. Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation. Neuroimmunomodulation. 2000;7(2):99-105. [Crossref] [PubMed]
- Park SG, Lee DY, Seo SK, Lee SW, Kim SK, Jung WK, et al. Evaluation of anti-allergic properties of caffeic acid phenethyl ester in a murine model of systemic anaphylaxis. Toxicol Appl Pharmacol. 2008;226(1):22-9. [Crossref] [PubMed]
- Jung WK, Lee DY, Choi YH, Yea SS, Choi I, Park SG, et al. Caffeic acid phenethyl ester attenuates allergic airway inflammation and hyperresponsiveness in murine model of ovalbumin-induced asthma. Life Sci. 2008;82(13-14):797-805. [Crossref] [PubMed]
- Bezerra RM, Veiga LF, Caetano AC, Rosalen PL, Amaral ME, Palanch AC, et al. Caffeic acid phenethyl ester reduces the activation of the nuclear factor κB pathway by high-fat diet-induced obesity in mice. Metabolism. 2012;61(11):1606-14. [Crossref] [PubMed]
- Yiğit U, Kırzıoğlu FY, Uğuz AC, Nazıroğlu M, Özmen Ö. Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis? Arch Oral Biol. 2017;81:61-8. [Crossref] [PubMed]
- Kızıldağ A, Arabacı T, Albayrak M, Taşdemir U, Şenel E, Dalyanoglu M, et al. Therapeutic effects of caffeic acid phenethyl ester on alveolar bone loss in rats with endotoxin-induced periodontitis. J Dent Sci. 2019;14(4):339-45. [Crossref] [PubMed] [PMC]
- Kızıldağ A, Arabacı T, Albayrak M, Balseven HM, Aksu Kızıldağ C, Tasdemir U. A biochemical and immunohistochemical study of the effects of caffeic acid phenethyl ester on alveolar bone loss and oxidative stress in diabetic rats with experimental periodontitis. Biotech Histochem. 2020;95(6):456-63. [Crossref] [PubMed]
- Otan Özden F, Lütfioğlu M, Demir E, Bilgici B. Antioxidant effect of caffeic acid phenethyl ester in experimentally induced periodontitis. Clin Oral Investig. 2021;25(8):4959-66. [Crossref] [PubMed]
- Graves DT, Kang J, Andriankaja O, Wada K, Rossa C Jr. Animal models to study host-bacteria interactions involved in periodontitis. Front Oral Biol. 2012;15:117-32. [Crossref] [PubMed] [PMC]
- Kador PF, O'Meara JD, Blessing K, Marx DB, Reinhardt RA. Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats. J Periodontol. 2011;82(6):926-33. [Crossref] [PubMed]
- Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 1993;329(1-2):21-4. [Crossref] [PubMed]
- Larki-Harchegani A, Hemmati AA, Arzi A, Ghafurian-Boroojerdnia M, Shabib S, Zadkarami MR, et al. Evaluation of the effects of caffeic acid phenethyl ester on prostaglandin E2 and two key cytokines involved in bleomycin-induced pulmonary fibrosis. Iran J Basic Med Sci. 2013;16(7):850-7. [PubMed] [PMC]
- Kantarci A, Hasturk H, Van Dyke TE. Host-mediated resolution of inflammation in periodontal diseases. Periodontol 2000. 2006;40:144-63. [Crossref] [PubMed]
- Salvi GE, Lang NP. Host response modulation in the management of periodontal diseases. J Clin Periodontol. 2005;32 Suppl 6:108-29. [Crossref] [PubMed]
- Stoyell KA, Mappus JL, Gandhi MA. Clinical efficacy of turmeric use in gingivitis: a comprehensive review. Complement Ther Clin Pract. 2016;25:13-7. [Crossref] [PubMed]
- Casati MZ, Algayer C, Cardoso da Cruz G, Ribeiro FV, Casarin RC, Pimentel SP, et al. Resveratrol decreases periodontal breakdown and modulates local levels of cytokines during periodontitis in rats. J Periodontol. 2013;84(10):e58-64. [Crossref] [PubMed]
- Corrêa MG, Pires PR, Ribeiro FV, Pimentel SP, Cirano FR, Napimoga MH, et al. Systemic treatment with resveratrol reduces the progression of experimental periodontitis and arthritis in rats. PLoS One. 2018;13(10):e0204414. [Crossref] [PubMed] [PMC]
- Choi EY, Choe SH, Hyeon JY, Choi JI, Choi IS, Kim SJ. Effect of caffeic acid phenethyl ester on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages. J Periodontal Res. 2015;50(6):737-47. [Crossref] [PubMed]
- Zekeridou A, Mombelli A, Cancela J, Courvoisier D, Giannopoulou C. Systemic inflammatory burden and local inflammation in periodontitis: what is the link between inflammatory biomarkers in serum and gingival crevicular fluid? Clin Exp Dent Res. 2019;5(2):128-35. [Crossref] [PubMed] [PMC]
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