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    Effects of combined systemic administration of low-dose doxycycline and alendronate on endotoxin-induced periodontitis in rats
    (2004) Buduneli E.; Vardar S.; Buduneli N.; Berdeli A.H.; Türkoglu O.; Başkesen A.; Atilla G.
    Background: Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2? (PGF2?), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in endotoxin-induced periodontal breakdown in rats. Methods: Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague-Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7-day study period. At the end of the 1-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2?, LTB4, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. Results: Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2 and PGF2?, (P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB4 and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05). Conclusions: Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice.
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    Effects of selective cyclooxygenase-2 inhibition on gingival tissue levels of prostaglandin E2 and prostaglandin F2? and clinical parameters of chronic periodontitis
    (2003) Vardar S.; Baylas H.; Huseyinov A.
    Background: The purpose of the present study was to evaluate the effect of a relatively selective cyclooxygenase (COX)-2 inhibitor (nimesulide) and non-selective COX-1/COX-2 inhibitor (naproxen) used as an adjunct to non-surgical (scaling and root planing [SRP]) periodontal therapy in chronic periodontitis patients on the gingival tissue (GT) levels of prostaglandin (PG)E2 and PGF2?. Methods: Thirty patients with chronic periodontitis were divided into 3 groups of 10 each. One group received 100 mg of nimesulide; one received 275 mg of naproxen sodium; and the third group received placebo tablets in a 2 _xt 1 regimen for 10 days as an adjunct to SRP. GT samples were obtained before drug intake and on day 10. Plaque index (PI) and papillary bleeding index (PBI) scores were recorded at baseline, day 10, and at 3 months; probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and at 3 months. The levels of PGE2 were detected using an enzyme immunoassay (EIA), and the levels of PGF2? were analyzed by radioimmunoassay (RIA). Differences among and within the groups were assessed using non-parametric statistical analysis. Ten periodontally healthy individuals served as controls. Results: All 3 groups showed statistically significant reductions in PBI and PI on day 10 and at 3 months (P <0.02), and in PD and CAL at 3 months (P <0.02, P <0.05, respectively). In the naproxen group, GT PGE2 levels exhibited a significant decrease (P <0.05). However, the decrease of GT PGE2 levels in the nimesulide group was insignificant (P >0.05), while a significant increase was observed in the placebo group (P <0.05) on day 10. Both the nimesulide and naproxen groups showed a significant decrease (P <0.05) in PGF2? level, while the placebo group showed a significant increase (P <0.05). Conclusions: Nimesulides, relatively selective COX-2 inhibitors, may have additional inhibitory effects on GT PGF2? levels in the first week following non-surgical periodontal treatment. However, nimesulide has an insignificant effect on reducing PGE2 levels in gingival tissue. The determination of GT levels of COX-1 and COX-2 enzymes as well as PGE2 and PGF2? in long-term studies may provide further support for the adjunctive use of selective COX-2 inhibitors in treatment of chronic periodontitis.
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    Individual and combined effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on endotoxin-induced periodontitis in rats
    (2005) Vardar S.; Buduneli E.; Baylas H.; Berdeli A.H.; Buduneli N.; Atilla G.
    Background: The present study was planned to evaluate the individual and combined effects of selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2? (PGF2?), leukotriene B4 (LTB4), and platelet activating factor (PAF) in endotoxin-induced periodontitis in rats. Methods: Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS). Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, celecoxib, omega-3 fatty acid, and combination celecoxib and omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given either as a single agent or as a combination therapy during 14 days of the study period. At the end of the 2-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2?, and LTB4 levels by enzyme immunoassay and for PAF levels by radioimmunoassay. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. Results: LPS injection resulted in significantly more bone loss than the saline controls (P<0.05) and significant elevations in the gingival tissue levels of all the analyzed mediators except PGF2?. Individual administration of celecoxib revealed significant reductions in PGE2 and PAF levels (P<0.05), while omega-3 fatty acid provided significant reduction in PGE2, PGF2?, and LTB4 levels compared to the LPS group (P <0.05). Combined administration of celecoxib and omega-3 fatty acid exhibited significantly lower values than those of the LPS group in all the analyzed membrane phospholipid mediators (P <0.05), which approximated the levels in the saline control group (P >0.05). Conclusions: The results of the present study indicate that celecoxib and omega-3 fatty acid, when used individually, show a rather partial effect on the control of the analyzed mediators, but when combined they show a synergic effect and provide significant reductions in the gingival tissue levels of PGE2, PGF2?, LTB4, and PAF in LPS-induced experimental periodontitis. These findings may pioneer further clinical human studies investigating the possible place of celecoxib and omega-3 fatty acid in periodontal treatment.
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    Therapeutic versus prophylactic plus therapeutic administration of omega-3 fatty acid on endotoxin-induced peridontitis in rats
    (2004) Vardar S.; Buduneli E.; Türkoglu O.; Berdeli A.H.; Baylas H.; Başkesen A.; Atilla G.
    Background: The aim of the present study was 1) to evaluate the possible effects of therapeutic usage of omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2? (PGF2?), platelet activating factor (PAF), and leukotriene B4 (LTB4) in endotoxin-induced periodontitis in rats and 2) to investigate whether prophylactic usage provides any additional benefits to therapeutic doses of omega-3 fatty acid. Methods: Experimental periodontitis was induced by repeated injection of Escherichia coli lipopolysaccharide (LPS). Thirty-six adult male Sprague-Dawley rats were divided into four study groups: 1) saline controls; 2) LPS; 3) therapeutic omega-3 fatty acid (TO3); and 4) prophylactic plus therapeutic omega-3 fatty acid (P + TO3) groups. In TO3 group, omega-3 fatty acid was given for 15 days following induction of experimental periodontitis. In P + TO3 group, omega-3 fatty acid was started 15 days before baseline, and then periodontitis was induced at baseline and omega-3 fatty acid was continued for 15 days after baseline. On day 15 after baseline, all rats were anesthetized and sacrificed. PGE2, PGF2?, and LTB4 levels in gingival tissue samples were analyzed by enzyme immunoassay and PAF levels were analyzed by radioimmonoassay. Data were evaluated statistically by using parametric tests. Results: LPS injection resulted in significant amount of bone loss (P <0.05). Neither therapeutic nor prophylactic plus therapeutic administration of omega-3 fatty acid with the doses and duration of therapy used in the present study was effective in preventing endotoxin-induced alveolar bone loss. TO3 group exhibited significant decreases in the gingival tissue levels of PGE2, PGF2?, LTB4, and PAF compared to the LPS group (P <0.05). PGE2 and PGF2? levels in TO3 group were similar to those of the saline group (P >0.05), while LTB4 and PAF levels were statistically higher than the saline group (P <0.05). Prophylactic plus therapeutic usage of omega-3 fatty acid provided similar levels of all these mediators to those of the saline controls (P >0.05). Conclusions: Therapeutic omega-3 fatty acid significantly reduced the gingival tissue levels of PGE2, PGF2?, LTB4, and PAF in experimental periodontitis. Furthermore, prophylactic usage of omega-3 fatty acid provided additional beneficial effects to the therapeutic administration by decreasing the gingival tissue levels of these mediators to levels of healthy tissue. These findings should be verified by longitudinal clinical trials investigating clinical and biochemical periodontal parameters to better define the possible role of omega-3 fatty acids in periodontal treatment.