(25-07-09) Tetradecanol Complex: Therapeutic Actions in Experimental Periodontitis

Hatice Hasturk,* Emilie Goguet-Surmenian,* Amanda Blackwood,* Chris Andry,? and Alpdogan Kantarci*
*Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, Boston, MA.
?Department of Pathology, School of Medicine, Boston University.
indicates supplementary slide presentation (with audio) in the online Journal of Periodontology.
Correspondence: Dr. Hatice Hasturk, Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, 100 East Newton St., Suite 107, Boston, MA 02118. Fax: 617/638-4799; e-mail: [email protected].
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ABSTRACT Section:

Background: The present study was planned to investigate the therapeutic actions of 1-tetradecanol complex (1-TDC), a novel monounsaturated fatty acid mixture, in established periodontitis in rabbits.
Methods: Periodontitis was initiated in 18 New Zealand White rabbits using ligatures around mandibular second premolars, followed by topical Porphyromonas gingivalis application (109 colony forming units). After 6 weeks of disease induction (phase 1), three animals were sacrificed to assess the established periodontitis level. P. gingivalis application was discontinued, and the remaining 15 animals continued with topical treatment of 1-TDC (100 mg/ml; n = 5) or placebo (n = 5) or no treatment (n = 5) for an additional 6 weeks (phase 2). Mandibular block sections obtained after euthanasia were decalcified and embedded in paraffin. In addition to the macroscopic analyses, hematoxylin and eosin?stained sections were used to study cellular inflammatory infiltrate and quantitative histomorphometry. Tartrate-resistant acid phosphatase and osteocalcin were used to identify osteoclastic and osteoblastic activity, respectively.
Results: P. gingivalis application resulted in periodontal disease with gingival inflammation and bone loss (30% compared to baseline) at 6 weeks. Treatment with 1-TDC stopped the progression of the disease and resulted in a significant reduction in the macroscopic periodontal inflammation, attachment, and bone loss (10.1% ? 1.8%), whereas periodontal disease progressed in the untreated and placebo groups (P <0.05). Histologic assessment and histomorphometric measurements demonstrated that 1-TDC inhibited inflammatory cell infiltration and osteoclastic activity (P <0.05).
Conclusion: The findings suggest that topical application of cetylated monounsaturated fatty acid complex (1-TDC) is a potential therapeutic approach in controlling the progression of chronic periodontal disease.
Host-mediated immune responses to microorganisms lead to the destruction of periodontal tissues.1-3 There is substantial evidence that the products of arachidonic acid (AA) metabolism may be pivotal in triggering and perpetuating the inflammatory changes seen in periodontitis.4-6 High concentrations of the AA-derived products leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) and inflammatory cytokines tumor necrosis factor-alpha and interleukin-1? and -6 are particularly destructive and implicated in periodontal diseases as well as other chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis.7-10 Manipulation of the immune response to suppress unwanted inflammatory reactions has been widely studied as a treatment for controlling such inflammatory responses in periodontal disease.11,12 Several host response?modulating approaches have been described;6 however, the control of inflammation with available pharmaceutical agents is still a challenge because of the side effects associated with their chronic use.
Fatty acids have been proposed to reduce chronic inflammation in individuals with arthritis by reducing the release of LTB4 from stimulated neutrophils and interleukin-1 from monocytes.13-15 The topical application of omega-3 (?-3) polyunsaturated fatty acid (PUFA) was successful in the treatment of inflammatory diseases, such as psoriasis, as well as experimental periodontitis in animal models by decreasing leukocyte chemotaxis, adhesion molecule expression, and inflammatory cytokine production.16-18 Offenbacher et al.19 showed that eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) can inhibit the production of PGE2 to an extent similar to ibuprofen when added to human periodontal homogenates. Pilot clinical and animal studies20-24 with ?-3 and ?-6 PUFA supplementation also showed beneficial results on periodontal inflammation and bone loss, indicating an anti-inflammatory role for these fatty acids without any evidence of the side effects often reported with the long-term use of non-steroidal anti-inflammatory drugs and other anti-inflammatory agents. However, the clinical studies22,24 with dietary supplements did not show significant influences on gingival and periodontal inflammation, most probably because of the lack of sufficient concentration of ?-3 PUFA locally when used in reasonable doses. Conversely, because of the high epithelial penetration of fatty acids,25 topical application may be favorable for the treatment of local oral inflammatory diseases, including periodontitis.26,27
Parallel to the findings with PUFAs, there is evidence suggesting that the substitution of monounsaturated fatty acids (MUFAs) for saturated fatty acids may favorably affect cardiovascular risk.28-30 Epidemiologic studies demonstrated the protective effects of MUFAs against coronary heart disease (CHD), and evidence from controlled clinical studies showed that MUFAs favorably affect a number of risk factors for CHD, including plasma lipids and lipoproteins, factors related to thrombogenesis, in vitro low-density lipoprotein oxidative susceptibility, and insulin sensitivity.30,31 Experimental evidence further suggests that MUFA-rich diets favorably influence blood pressure, coagulation, endothelial activation, inflammation, and thermogenic capacity.32 MUFAs are also beneficial for the prevention of obesity and other metabolic diseases and for immune function.33 Recently, we showed that the topical application of 1-tetradecanol complex (1-TDC), a novel MUFA that contains a blend of esterified MUFAs, is capable of protecting from inflammatory changes in experimental periodontitis induced by Porphyromonas gingivalis in rabbits.34 1-TDC was effective in preventing gingival inflammation by controlling the inflammatory cascade initiated by the periodontal pathogen P. gingivalis and further protected from more destructive forms of periodontal inflammation.34 In this study, we tested the hypothesis that MUFA-induced control of inflammation halts the destruction of periodontal tissues after active disease is established.

Source: Journal of Periodontology 2009, Vol. 80, No. 7, Pages 1103-1113 , DOI 10.1902/jop.2009.090002

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