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

Autor: Araújo AA; Department of Biophysics and Pharmacology, Post Graduation Program Public Health / Post Graduation Program in Pharmaceutical Science, UFRN, Natal, RN, Brazil., Pereira ASBF; Post Graduation Program Public Health, UFRN, Natal, RN, Brazil., Medeiros CACX; Department of Biophysics and Pharmacology,Post Graduation Program RENORBIO,/Post Graduation Program Biological Science, UFRN, Natal, RN, Brazil., Brito GAC; Department of Morphology, Post Graduation Program in Morphology, UFC, Fortaleza, Ceará, Brazil., Leitão RFC; Department of Morphology, Post Graduation Program in Morphology, UFC, Fortaleza, Ceará, Brazil., Araújo LS; Post Graduation Program Public Health, UFRN, Natal, RN, Brazil., Guedes PMM; Department of Microbiology and Parasitology, Post Graduation Program in Parasitary Biology/Post Guaduation Biological Science, UFRN, Natal, RN, Brazil., Hiyari S; Section of Periodontics, School of Dentistry, University of California, UCLA, Los Angeles, California, United States of America., Pirih FQ; Section of Periodontics, School of Dentistry, University of California, UCLA, Los Angeles, California, United States of America., Araújo Júnior RF; Department of Morphology, Post Graduation Program in Functional and Structural Biology/ Post Graduation Program Health Science/Department of Morphology, UFRN, Natal, RN, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 Aug 28; Vol. 12 (8), pp. e0183506. Date of Electronic Publication: 2017 Aug 28 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0183506
Abstrakt: 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.
Databáze: MEDLINE
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