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 local administration of tiludronic acid on experimental periodontitis in diabetic rats.

BACKGROUND: Tiludronic acid (TIL) presents antiresorptive and anti-inflammatory properties and has not been evaluated in the periodontitis-diabetes mellitus (DM) association to date, to the best knowledge of the authors. This study evaluates effects of local administration of TIL on experimental periodontitis (EP) in rats with streptozotocin-induced DM. METHODS: Thirty-two animals (Rattus norvegicus albinus, Wistar) were divided into groups DM/C (Control), DM/EP, DM/EP/TIL1, and DM/EP/TIL3. In EP groups, a ligature was placed around mandibular first molars. In groups DM/EP/TIL1 and DM/EP/TIL3, TIL solutions (1 and 3 mg/kg, respectively) were injected into the gingival tissue of mandibular molars every other day for 10 days, until euthanasia. Periodontal tissues were analyzed by microcomputed tomography (micro-CT), histomorphometry, immunohistochemistry (tartrate-resistant acid phosphatase [TRAP], receptor activator of nuclear factor-κB ligand [RANKL], osteoprotegerin, cleaved caspase 3), and quantitative reverse transcription-polymerase chain reaction (interleukin [IL]-1ß, vascular endothelial growth factor [VEGF]). RESULTS: In micro-CT analyses, groups DM/EP/TIL1 and DM/EP/TIL3 presented reduced alveolar bone resorption (P < 0.05). Group DM/EP/TIL3 presented decreased attachment loss (P < 0.05). The amount of TRAP-positive multinucleated cells was decreased in TIL groups (P < 0.05). Group DM/EP/TIL3 presented a lower immunolabeling pattern for RANKL (P < 0.05). TIL treatment decreased genic expression of IL-1ß, and in group DM/EP/TIL3, expression of VEGF was increased (P < 0.05). CONCLUSION: Local administration of TIL promoted a protective effect against tissue destruction in EP in diabetic rats, and the dosage of 3 mg/kg of TIL promoted the best results regarding its antiresorptive and anti-inflammatory effects.

Effects of electroacupuncture on experimental periodontitis in rats.

BACKGROUND: Acupuncture has shown the capability of modulating the immuno-inflammatory response of the host. This study aims to evaluate the effects of electroacupuncture (EA) on ligature-induced periodontitis in rats. METHODS: Thirty-two animals were divided into four groups: 1) control; 2) experimental periodontitis (EP); 3) sham-treated (EP/EA-sham); and 4) treated with EA (EP/EA). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. For EA treatment, large intestine meridian points LI4 and LI11 and stomach meridian points ST36 and ST44 were used. EA-sham was performed in off-meridian points. Animals were euthanized at day 11. Histomorphometric and microtomographic analyses were performed. Immunolabeling patterns for the receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) were assessed. Expressions of interleukin (IL)-1ß, matrix metalloproteinase (MMP)-8, IL-6, and cyclooxygenase (COX)-2 messenger RNAs (mRNAs) were evaluated by quantitative reverse transcription-polymerase chain reaction. Data were analyzed statistically (P <0.05, analysis of variance). RESULTS: Histomorphometric and microtomographic analyses demonstrated that group EP/EA presented reduced alveolar bone loss when compared to group EP (P <0.05). Reduced RANKL immunolabeling and fewer TRAP-positive multinucleated cells were observed in the EA-treated group in relation to group EP. No differences were observed in OPG expression among groups. EA treatment decreased the genic expression of IL-1ß and MMP-8 (P <0.05), increased the mRNA expression of IL-6 (P <0.05), and did not modify the genic expression of COX-2 in animals with EP (P >0.05). CONCLUSION: It can be concluded that EA reduced periodontal tissue breakdown and the expression of some proinflammatory mediators and a proresorptive factor in EP 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.