PLoS ONE (Jan 2017)

Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis.

  • Aurigena Antunes de Araújo,
  • Aline de Sousa Barbosa Freitas Pereira,
  • Caroline Addison Carvalho Xavier de Medeiros,
  • Gerly Anne de Castro Brito,
  • Renata Ferreira de Carvalho Leitão,
  • Lorena de Souza Araújo,
  • Paulo Marcos Matta Guedes,
  • Sarah Hiyari,
  • Flávia Q Pirih,
  • Raimundo Fernandes de Araújo Júnior

DOI
https://doi.org/10.1371/journal.pone.0183506
Journal volume & issue
Vol. 12, no. 8
p. e0183506

Abstract

Read online

To evaluate the effects of metformin (Met) on inflammation, oxidative stress, and bone loss in a rat model of ligature-induced periodontitis.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.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.Metformin, at a concentration of 50 mg/kg, decreases the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats.