title: The effect of spironolactone on experimental periodontitis in rats.
abstract: BACKGROUND
  Elevated levels of tumour necrosis factor (TNF) have been found in patients with adult periodontitis. Animal studies have shown that TNF plays an important role in the pathogenesis of periodontitis. New findings suggest that the aldosterone-inhibitor spironolactone possesses an anti-TNF effect. The purpose of the study was to determine the anti-TNF effect of spironolactone in an endotoxic shock rat model and to disclose the effect of oral administration of spironolactone on the development of experimental periodontitis in rats.
  
  
  METHODS
  The study was divided in two parts. Part 1: oral administration of spironolactone (100 mg/kg) followed by intravenous lipopolysaccharide (1 mg/kg) infusion 45 min later. Blood samples were taken before and 90 min after lipopolysaccharide infusion to determine the TNF levels in spironolactone treated and non-treated rats. Part 2: oral administration of spironolactone [100 mg/(kg day)] starting 2 days prior to induction of experimental periodontitis established by peridental ligatures. Morphometrical and radiographical registrations of alveolar bone destruction were carried out to determine the effect of spironolactone on the progression of experimental periodontitis.
  
  
  RESULTS
  In part 1 the endotoxic shock model showed a significant reduction in TNF levels in the spironolactone-treated group compared to the non-treated group, suggesting that spironolactone acts as a TNF inhibitor. In part 2 spironolactone-treated rats did not demonstrate significantly less alveolar bone destruction compared to non-treated rats.
  
  
  CONCLUSIONS
  The insignificant effect of spironolactone treatment could be explained by the fast metabolism of spironolactone and that spironolactone does not completely inhibit TNF production in rats. Moreover, many other cytokines and mediators involved in alveolar bone destruction may account for the lacking response to spironolactone.
authors.affiliation: Department of Periodontology, School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M C B
authors.initials: MC
authors.lastname: Grauballe
authors.forename: B H
authors.initials: BH
authors.lastname: Bentzen
authors.forename: M
authors.initials: M
authors.lastname: Björnsson
authors.forename: D
authors.initials: D
authors.lastname: Moe
authors.forename: T E N
authors.initials: TE
authors.lastname: Jonassen
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
authors.forename: K
authors.initials: K
authors.lastname: Stoltze
authors.forename: P
authors.initials: P
authors.lastname: Holmstrup
mesh_terms: D000284:Administration, Oral; D016301:Alveolar Bone Loss / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008439:Maxillary Diseases / Q000188:drug therapy / Q000517:prevention & control; D010518:Periodontitis / Q000188:drug therapy*; D051381:Rats; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy*; D013148:Spironolactone / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013148:Spironolactone