Nara L T Nunes1, Michel R Messora2, Luiz Fernando Oliveira2, Mario Lisboa3, Marina Costa Barcellos Garcia2, R O Rêgo4, Arthur Belém Novaes2, Sérgio Luís Scombatti de Souza2, Edilson Ervolino5, Flávia A C Furlaneto2. 1. Department of Clinical Dentistry, Graduate Program in Dentistry, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza, Ceará, Brazil. 2. Department of Oral and Maxillofacial Surgery and Periodontology, School of Dentistry of Ribeirao Preto, University of São Paulo, Ribeirao Preto, São Paulo, Brazil. 3. Department of Morphology, Faculty of Medicine, Federal University of Ceará. 4. Department of Dentistry, School of Dentistry at Sobral, Federal University of Ceará, Sobral, Ceará, Brazil. 5. Department of Basic Sciences, Division of Histology, Dental School of Araçatuba, São Paulo State University, Araçatuba , São Paulo, Brazil.
Abstract
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]-1β, 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-1β, 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.
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]-1β, 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-1β, 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 diabeticrats, and the dosage of 3 mg/kg of TIL promoted the best results regarding its antiresorptive and anti-inflammatory effects.
Authors: Xiaobei Wang; Zhenshan Jia; Yosif Almoshari; Subodh M Lele; Richard A Reinhardt; Dong Wang Journal: Pharm Res Date: 2018-06-25 Impact factor: 4.200