title: Cimetidine reduces alveolar bone loss in induced periodontitis in rat molars.
abstract: BACKGROUND
  There is evidence that histamine released during inflammation plays a role in bone metabolism via the H2 receptor, stimulating bone resorption. The purpose of this study is to evaluate whether cimetidine, a histamine H2-receptor antagonist, interferes with the initiation and progression of induced periodontal disease in rat molars.
  
  
  METHODS
  Forty male rats received 100 mg/kg body weight of cimetidine (cimetidine group [CimG]) or saline solution (sham group [SG]). Periodontal disease was induced in the maxillary left first molars (PDSG and PDCimG); maxillary right molars were used as non-ligature controls. After 7, 15, 30, and 50 days, maxillary fragments were embedded in paraffin. The sections were stained with Masson trichrome and hematoxylin and eosin and subjected to the tartrate-resistant acid phosphatase (TRAP) method. The distances between the cemento-enamel junction (CEJ) and alveolar process (AP) crest, as well as between the CEJ and junctional epithelium (JE) level, were measured; the number of inflammatory cells was computed. Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) immunohistochemistry was carried out, and the RANKL/OPG ratio was calculated.
  
  
  RESULTS
  In PDSG and PDCimG, a significant increase (P ≤0.05) was observed in CEJ-AP and CEJ-JE distances. However, the increases in both distances were significantly less in PDCimG compared with PDSG at 15, 30, and 50 days. Numerous TRAP-positive osteoclasts were found in the PDSG and PDCimG. In PDCimG, the volume density of inflammatory cells and the RANKL/OPG ratio were significantly lower (P ≤0.05) than in PDSG.
  
  
  CONCLUSIONS
  Cimetidine exerts a beneficial effect on periodontal disease in rats, decreasing the RANKL/OPG ratio in gingival connective tissue and reducing alveolar bone resorption.
authors.affiliation: Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Longhini
authors.forename: Priscila
authors.initials: P
authors.lastname: Aparecida de Oliveira
authors.forename: Estela
authors.initials: E
authors.lastname: Sasso-Cerri
authors.forename: Paulo Sérgio
authors.initials: PS
authors.lastname: Cerri
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D016301:Alveolar Bone Loss / Q000473:pathology / Q000517:prevention & control*; D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000818:Animals; D002927:Cimetidine / Q000627:therapeutic use*; D004396:Coloring Agents; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004846:Epithelial Attachment / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005881:Gingiva / Q000187:drug effects / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008437:Maxilla; D008963:Molar; D053244:Osteoprotegerin / Q000032:analysis / Q000187:drug effects; D010518:Periodontitis / Q000473:pathology / Q000517:prevention & control*; D053245:RANK Ligand / Q000032:analysis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors; D019237:Tooth Cervix / Q000187:drug effects / Q000473:pathology
chemical_list: D004396:Coloring Agents; D006635:Histamine H2 Antagonists; D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D002927:Cimetidine; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Alveolar process; RANK ligand; cimetidine; gingiva; osteoprotegerin; periodontitis