Local administration of Tiludronic Acid downregulates important mediators involved in periodontal tissue destruction in experimental periodontitis in rats.

OBJECTIVE: The purpose of this study was to evaluate whether local administration of TIL could influence the expression of the inflammatory mediators IL-1ß, TNF-α, MMP-8 and COX-2 in rats with experimental periodontitis (EP). METHODS: Twenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to groups C, EP, EP-TIL (CControl group, EP-Periodontitis groups). On EP groups, a ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 µL of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal area adjacent to the maxillary 2nd molar every other day until euthanasia (day 11). Alveolar bone loss was morphometrically analyzed. mRNA expressions of IL-1ß, TNF-α, MMP-8 and COX-2 were assessed by qPCR. IL-1ß, TNF-α, MMP-8 and COX-2 were immunohistochemically analyzed. Data were analyzed statistically. RESULTS: Group EP-TIL presented reduced alveolar bone loss when compared with group EP (p < 0.05). Group EP-TIL presented decreased mRNA expressions of IL-1ß, TNF-α, MMP-8 and COX-2 and reduced immunolabeling of IL-1ß, TNF-α and MMP-8 when compared with group EP (p < 0.05). No differences regarding the immunolabeling of COX-2 were found when group EP-TIL was compared with the other groups (p > 0.05). CONCLUSION: Within the limits of this study, it can be concluded that local administration of TIL downregulates important mediators involved in periodontal tissue destruction in ligature-induced periodontitis in rats.

Effects of locally administered tiludronic acid on experimental periodontitis in rats.

BACKGROUND: It appears there are no studies evaluating the influence of the bisphosphonate tiludronic acid (TIL) on periodontitis. The purpose of this study is to evaluate via microtomographic, histopathologic, histometric, and immunohistochemical analyses the effects of local administration of TIL on ligature-induced periodontitis in rats. METHODS: Forty-eight rats were divided into six groups: C (control), EP (experimental periodontitis), EP-Saline, EP-TIL0.1, EP-TIL0.3, and EP-TIL1. In EP, a ligature was placed around maxillary second molars. In EP-TIL0.1, EP-TIL0.3, and EP-TIL1, TIL solutions of 0.1, 0.3, and 1 mg/kg body weight, respectively, were injected into the subperiosteal palatal area adjacent to maxillary second molars every other day. EP-Saline received 0.9% NaCl solution instead. Animals were euthanized at day 11. Bone changes were evaluated by microtomographic and histometric analyses. Histopathologic analysis and immunohistochemical detection of tartrate-resistant acid phosphatase (TRAP) were also performed. Data were statistically analyzed (analysis of variance or Kruskal-Wallis, P <0.05). RESULTS: Histometric and microtomographic analyses (at buccal, interproximal, and furcation sites) demonstrated that EP-TIL1 presented less alveolar bone loss (ABL) than EP (P <0.05), whereas EP-TIL0.1 and EP-TIL0.3 did not demonstrate significant differences in alveolar bone level compared to EP (P >0.05). Also, EP-TIL1 showed significantly fewer TRAP-positive multinucleated osteoclasts than EP and EP-Saline (P <0.05). CONCLUSION: It can be concluded that locally administered TIL solution (1 mg/kg body weight) reduced alveolar bone loss in experimental periodontitis and the dosage of TIL may influence its anti-inflammatory and antiresorptive properties.