Low-dose doxycycline and alendronate in endotoxin-induced periodontitis in rats

Objectives: Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Recently, biphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and a biphosphonate; alendronate on gingival tissue levels of prostaglandin E₂ (PGE₂), prostaglandin F_2a (PGF_2a), 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 forty-four adult male Sprague-Dawley rats were divided into 5 study groups as follows; LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate was given either as a single agent or as a combination therapy during 7 days of the experimental study period. At the end of 1-week protocol, rats were sacrificed, the gingival tissues were extracted and the extracts were analyzed for PGE₂, PGF_2a, LTB₄ and PAF levels. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by 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 PGF_2a (P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB₄ and PAF levels, although doxycycline provided the most reduction in levels of these mediators (P<0.05). Conclusions: Alendronate and/or doxycycline may provide significant inhibition of major inflammatory mediators of periodontal tissue destruction and particularly 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 their use in dental practice.