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Title: Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis
Authors: Araújo, Aurigena Antunes de
Pereira, Aline de Sousa Barbosa Freitas
Medeiros, Caroline Addison Carvalho Xavier de
Brito, Gerly Anne de Castro
Leitão, Renata Ferreira de Carvalho
Araújo, Lorena de Souza
Guedes, Paulo Marcos Matta
Hiyari, Sarah
Pirih, Flávia Q.
Araújo Júnior, Raimundo Fernandes de
Keywords: Oxidative stress;Metformin on inflammation
Issue Date: 28-Aug-2017
Publisher: Charles P. Darby Children's Research Institute, UNITED STATES
Citation: ARAÚJO, Aurigena Antunes de et al. Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis. PLoS One, v. 12, p. 1-21, 2017. Disponível em: <>. Acesso em: 21 mar. 2018.
Portuguese Abstract: Aim To evaluate the effects of metformin (Met) on inflammation, oxidative stress, and bone loss in a rat model of ligature-induced periodontitis. Materials & methods Male albino Wistar rats were divided randomly into five groups of twenty-one rats each, and given the following treatments for 10 days: (1) no ligature + water, (2) ligature + water, (3) ligature + 50 mg/kg Met, (4) ligature + 100 mg/kg Met, and (5) ligature + 200 mg/kg Met. Water or Met was administered orally. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantitate linear and bone volume/tissue volume (BV/TV) volumetric bone loss. Histopathological characteristics were assessed through immunohistochemical staining for MMP-9, COX-2, the RANKL/RANK/OPG pathway, SOD-1, and GPx-1. Additionally, confocal microscopy was used to analyze osteocalcin fluorescence. UV-VIS analysis was used to examine the levels of malondialdehyde, glutathione, IL-1β and TNF-α from gingival tissues. Quantitative RT-PCR reaction was used to gene expression of AMPK, NF-κB (p65), and Hmgb1 from gingival tissues. Significance among groups were analysed using a one-way ANOVA. A p-value of p<0.05 indicated a significant difference. Results Treatment with 50 mg/kg Met significantly reduced concentrations of malondialdehyde, IL-1β, and TNF-α (p < 0.05). Additionally, weak staining was observed for COX-2, MMP-9, RANK, RANKL, SOD-1, and GPx-1 after 50 mg/kg Met. OPG and Osteocalcin showed strong staining in the same group. Radiographically, linear measurements showed a statistically significant reduction in bone loss after 50 mg/kg Met compared to the ligature and Met 200 mg/kg groups. The same pattern was observed volumetrically in BV/TV and decreased osteoclast number (p<0.05). RT-PCR showed increased AMPK expression and decreased expression of NF-κB (p65) and HMGB1 after 50 mg/kg Met. Conclusions Metformin, at a concentration of 50 mg/kg, decreases the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats.
ISSN: 1932-6203
Appears in Collections:CB - DBF - Artigos publicados em periódicos
CB - DMOR - Artigos publicados em periódicos

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