Cimetidine (histamine H2-receptor antagonist and antiandrogenic drug) exerts a beneficial effect in the injured tissues by periodontal disease in male rat molars
R. Longhini2, P. de Oliveira1, E. Sasso-Cerri1 & P. Cerri1
Studies have demonstrated the presence of androgen receptors in osteoblasts and osteocytes, confirming that androgens are important for the maintenance of bone in men. Additionally to steroid hormones, histamine stimulates osteoclast differentiation and survival and plays a role in the inflammatory response via H2 receptors. We purposed to investigate whether cimetidine, an histamine H2 receptors antagonist and antiandrogenic drug, interferes in the periodontal tissue damages induced by periodontal disease (PD). PD was induced in the upper left first molars of male rats. Two PD groups (n=8 per group) were treated with 100 mg/kg bw of cimetidine (PD-Cim) or saline (PD-S), for 50 days. The right molars were used as controls: Cim and S groups, respectively. Blood samples were collected for detection of testosterone levels and the fragments of maxilla were removed and fixed in formaldehyde, decalcified in EDTA, and embedded in paraffin. Some fragments were processed for transmission electron microscopy (TEM). In HE-stained sections, the distances between cemento-enamel junction (CEJ) and the AB crest, as well as CEJ and junctional epithelium insertion level (JE) were measured; the number of inflammatory cells was also computed. TRAP method (osteoclast marker) was used for quantification of osteoclasts in the AB surface. Statistical analyses were performed (P≤0,05). Testosterone levels decreased significantly in cimetidine-treated rats. The significant increase in both CEJ-AB crest and CEJ-JE distances, observed in PD groups, were significantly softened in PD-Cim group. In Cim and PD-Cim groups, osteoclasts number decreased significantly in comparison to S and PD-S, respectively. Moreover, these cells exhibited apoptotic features under TEM. The inflammatory process reduced significantly in PD-Cim group. Although reduced testosterone levels promote osteoporosis, cimetidine treatment was able to reduce PD-induced periodontal tissue injuries. The possible histamine H2 receptors antagonist effect should be considered.
Financial Support: FAPESP (2010/10391-9; 2010/03571-0), CNPq (304794/2009-0) Brazil.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.