title: Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats.
abstract: BACKGROUND
  To study aldose reductase and the sorbitol pathway in periodontitis and diabetes, rats with experimental periodontitis with or without diabetes were treated with three structurally diverse aldose reductase inhibitors (ARIs).
  
  
  METHODS
  Periodontitis was induced with three consecutive palatal injections of Porphyromonas gingivalis lipopolysaccharide (LPS) at 48-hour intervals between the first and second molars on the right side in young, age-matched, streptozotocin-induced rats with and without diabetes 44 days after initiation of diets with and without the ARIs tolrestat, imirestat, and quercetin. As an internal control, phosphate-buffered saline (PBS) was similarly injected on the left side. Twenty-four days after the final injection, all rats were euthanized. Defleshed samples were stained with 5% toluidine blue and palatal digital images were traced to include the enamel crown and exposed root. The root/enamel ratios (to estimate alveolar bone loss) were analyzed with repeated measures analysis of variance.
  
  
  RESULTS
  LPS injections resulted in significantly more bone loss versus PBS injections in both the rats with and without diabetes on normal diets (P <0.0001). All three ARIs significantly reduced LPS-induced periodontitis in the animals with and without diabetes (P ≤0.003) to the level where they were not different from PBS-injected sites in normal diet controls.
  
  
  CONCLUSIONS
  All ARIs demonstrated efficacy in preventing alveolar bone loss because of periodontitis in both animals with and without diabetes, suggesting a role for the sorbitol pathway and the potential for ARIs to reduce inflammatory responses downstream from aldose reductase.
authors.affiliation: Therapeutic Vision, Omaha, NE, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Kador
authors.forename: James D
authors.initials: JD
authors.lastname: O'Meara
authors.forename: Karen
authors.initials: K
authors.lastname: Blessing
authors.forename: David B
authors.initials: DB
authors.lastname: Marx
authors.forename: Richard A
authors.initials: RA
authors.lastname: Reinhardt
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002952:Citric Acid Cycle; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005449:Fluorenes / Q000627:therapeutic use; D006019:Glycolysis; D006827:Hydantoins / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008297:Male; D009281:Naphthalenes / Q000627:therapeutic use; D010518:Periodontitis / Q000150:complications / Q000188:drug therapy*; D011794:Quercetin / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005449:Fluorenes; D006827:Hydantoins; D008070:Lipopolysaccharides; D009281:Naphthalenes; C052241:imirestat; C040550:tolrestat; D013012:Sorbitol; D011794:Quercetin; D000449:Aldehyde Reductase