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

Abstract

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. 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 3mg/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]-1β, vascular endothelial growth factor [VEGF]). 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-1β, and in group DM/EP/TIL3, expression of VEGF was increased (P<0.05). Local administration of TIL promoted a protective effect against tissue destruction in EP in diabetic rats, and the dosage of 3mg/kg of TIL promoted the best results regarding its antiresorptive and anti-inflammatory effects.