Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Processo FAPESP: 10/10391-9

Processo FAPESP: 10/03571-0

Processo FAPESP: 07/59374-6

Background: There is evidence that histamine released during inflammation plays a role in bone metabolism via the H-2 receptor, stimulating bone resorption. The purpose of this study is to evaluate whether cimetidine, a histamine H-2-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.