title: Effects of combined systemic administration of low-dose doxycycline and alendronate on endotoxin-induced periodontitis in rats.
abstract: 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 F2alpha (PGF2alpha), 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, PGF2alpha, 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 PGF2alpha (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.
authors.affiliation: Ege University, School of Dentistry, Department of Periodontology, Izmir, Turkey. eralp@bornova.ege.edu.tr
authors.forename: Eralp
authors.initials: E
authors.lastname: Buduneli
authors.forename: Saynur
authors.initials: S
authors.lastname: Vardar
authors.forename: Nurcan
authors.initials: N
authors.lastname: Buduneli
authors.forename: Afig Huseyinov
authors.initials: AH
authors.lastname: Berdeli
authors.forename: Oya
authors.initials: O
authors.lastname: Türkoğlu
authors.forename: Aykut
authors.initials: A
authors.lastname: Başkesen
authors.forename: Gül
authors.initials: G
authors.lastname: Atilla
mesh_terms: D019386:Alendronate / Q000627:therapeutic use*; D016301:Alveolar Bone Loss / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004318:Doxycycline / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004731:Endotoxins; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D010518:Periodontitis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D010972:Platelet Activating Factor; D007975:Leukotriene B4; C044101:endotoxin, Escherichia coli; D015237:Dinoprost; D015232:Dinoprostone; D004318:Doxycycline; D019386:Alendronate