Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model

Authors

  • Aurigena Antunes de Araújo Universidade Federal do Rio Grande do Norte, Programa de Pós-Graduação em Ciências Farmacêuticas, Programa de Pós-Graduação em Saúde Pública, Departamento de Biofísica e Farmacologia https://orcid.org/0000-0001-9264-4695
  • Helicarlos Batista de Morais Universidade Federal do Rio Grande do Norte, Programa de Pós-Graduação em Saúde Pública https://orcid.org/0000-0003-2050-1542
  • Caroline Adisson Carvalho Xavier de Medeiros 3 Universidade Federal do Rio Grande do Norte, Programa de Pós-Graduação RENORBIO, Programa de Pós-Graduação em Biologia, Departamento de Biofísica e Farmacologia https://orcid.org/0000-0001-9224-2434
  • Gerly Anne de Castro Brito Universidade Federal do Ceará, Programa de Pós-Graduação em Farmacologia, Programa de PósGraduação em Morfologia, Departamento de Morfologia https://orcid.org/0000-0002-8214-4379
  • Paulo Marcos Matta Guedes Universidade Federal do Rio Grande do Norte, Programa de Pós-Graduação em Biologia Parasitária, Departamento de Microbiologia e Parasitologia https://orcid.org/0000-0002-4564-6791
  • Sarah Hiyari University of California, School of Dentistry, Section of Periodontics https://orcid.org/0000-0002-3313-9418
  • Flávia Q. Pirih 6 University of California, School of Dentistry, Section of Periodontics https://orcid.org/0000-0003-1670-7345
  • Raimundo Fernandes de Araújo Júnior Universidade Federal do Rio Grande do Norte, Departamento de Morfologia, Porgrama de PósGraduação em Biologia Funcional e Estrutural, Programa de Pós-Graduação em Ciências da Saúde https://orcid.org/0000-0003-2349-2354

DOI:

https://doi.org/10.1590/1678-7757-2018-0211

Keywords:

Periodontitis, Inflammation, Bone, Micro-computed tomography, Cytokines

Abstract

Objective: The aim of this study was to evaluate the effects of gliclazide on oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. Material and Methods: Male albino Wistar rats were divided into no ligature, ligature, and ligature with 1, 5, and 10 mg/kg gliclazide groups. Maxillae were fixed and scanned using micro-computed tomography to quantify linear and bone volume/tissue volume (BV/TV) and volumetric bone loss. Histopathological, immunohistochemical and immunofluorescence analyses were conducted to examine matrix metalloproteinase-2 (MMP-2), cyclooxygenase 2 (COX-2), cathepsin K, members of the receptor activator of the nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor kappa-Β (RANK), osteoprotegerin (OPG) pathway, macrophage migration inhibitory factor (MIF), superoxide dismutase-1 (SOD-1), glutathione peroxidase-1 (GPx-1), NFKB p 50 (Cytoplasm), NFKB p50 NLS (nuclear localization signal), PI3 kinase and AKT staining. Myeloperoxidase activity, malondialdehyde and glutathione levels, while interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. A quantitative reverse transcription polymerase chain reaction was used to quantify the gene expression of the nuclear factor kappa B p50 subunit (NF-κB p50), phosphoinositide 3-kinase (PI3k), protein kinase B (AKT), and F4/80. Results: Micro-computed tomography showed that the 1 mg/kg gliclazide treatment reduced linear bone loss compared to the ligature, 5 mg/kg gliclazide, and 10 mg/kg gliclazide treatments. All concentrations of gliclazide increased bone volume/tissue volume (BV/TV) compared to the ligature group. Treatment with 1 mg/kg gliclazide reduced myeloperoxidase activity, malondialdehyde, IL-1β, and TNF-α levels (p≤0.05), and resulted in weak staining for COX-2, cathepsin k, MMP-2, RANK, RANKL, SOD-1, GPx-1,MIF and PI3k. In addition, down-regulation of NF-κB p50, PI3k, AKT, and F4/80 were observed, and OPG staining was strong after the 1 mg/ kg gliclazide treatment. Conclusions: This treatment decreased neutrophil and macrophage migration, decreased the inflammatory response, and decreased bone loss in rats with ligature-induced periodontitis.

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Published

2019-06-04

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Section

Original Articles