RESEARCH ARTICLE

Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis Aurigena Antunes de Arau´jo1*, Aline de Sousa Barbosa Freitas Pereira2, Caroline Addison Carvalho Xavier de Medeiros3, Gerly Anne de Castro Brito4, Renata Ferreira de Carvalho Leitão4, Lorena de Souza Arau´jo5, Paulo Marcos Matta Guedes6, Sarah Hiyari7, Fla´via Q. Pirih7, Raimundo Fernandes de Arau´jo Ju´nior8

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1 Department of Biophysics and Pharmacology, Post Graduation Program Public Health / Post Graduation Program in Pharmaceutical Science, UFRN, Natal, RN, Brazil, 2 Post Graduation Program Public Health, UFRN, Natal, RN, Brazil, 3 Department of Biophysics and Pharmacology,Post Graduation Program RENORBIO,/Post Graduation Program Biological Science, UFRN, Natal, RN, Brazil, 4 Department of Morphology, Post Graduation Program in Morphology, UFC, Fortaleza, Ceara´, Brazil, 5 Post Graduation Program Public Health, UFRN, Natal, RN, Brazil, 6 Department of Microbiology and Parasitology, Post Graduation Program in Parasitary Biology/Post Guaduation Biological Science, UFRN, Natal, RN, Brazil, 7 Section of Periodontics, School of Dentistry, University of California, UCLA, Los Angeles, California, United States of America, 8 Department of Morphology, Post Graduation Program in Functional and Structural Biology/ Post Graduation Program Health Science/Department of Morphology, UFRN, Natal, RN, Brazil * [email protected]

OPEN ACCESS Citation: Arau´jo AAd, Pereira AdSBF, Medeiros CACXd, Brito GAdC, Leitão RFdC, Arau´jo LdS, et al. (2017) Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis. PLoS ONE 12(8): e0183506. https:// doi.org/10.1371/journal.pone.0183506 Editor: Sakamuri V. Reddy, Charles P. Darby Children’s Research Institute, UNITED STATES Received: March 21, 2017

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

Accepted: August 4, 2017 Published: August 28, 2017 Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was funded by CNPq, 401838/ 2016-1.

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

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

To evaluate the effects of metformin (Met) on inflammation, oxidative stress, and bone loss in a rat model of ligature-induced periodontitis...
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