Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis

Periodontal diseases are initiated primarily by Gram-negative, tooth-associated microbial biofilms that elicit a host response that causes osseous and soft tissue destruction. Carvedilol is a β-blocker used as a multifunctional neurohormonal antagonist that has been shown to act not only as an anti-...

Full description

Bibliographic Details
Main Authors: de Araújo Júnior, Raimundo Fernandes, Souza, Tatiana Oliveira, de Medeiros, Caroline Addison Xavier, de Souza, Lélia Batista, Freitas, Maria de Lourdes, de Lucena, Hévio Freitas, do Socorro Costa Feitosa Alves, Maria, de Araújo, Aurigena Antunes
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700994/
id pubmed-3700994
recordtype oai_dc
spelling pubmed-37009942013-07-10 Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis de Araújo Júnior, Raimundo Fernandes Souza, Tatiana Oliveira de Medeiros, Caroline Addison Xavier de Souza, Lélia Batista Freitas, Maria de Lourdes de Lucena, Hévio Freitas do Socorro Costa Feitosa Alves, Maria de Araújo, Aurigena Antunes Research Article Periodontal diseases are initiated primarily by Gram-negative, tooth-associated microbial biofilms that elicit a host response that causes osseous and soft tissue destruction. Carvedilol is a β-blocker used as a multifunctional neurohormonal antagonist that has been shown to act not only as an anti-oxidant but also as an anti-inflammatory drug. This study evaluated whether Carvedilol exerted a protective role against ligature-induced periodontitis in a rat model and defined how Carvedilol affected metalloproteinases and RANKL/RANK/OPG expression in the context of bone remodeling. Rats were randomly divided into 5 groups (n = 10/group): (1) non-ligated (NL), (2) ligature-only (LO), and (3) ligature plus Carvedilol (1, 5 or 10 mg/kg daily for 10 days). Periodontal tissue was analyzed for histopathlogy and using immunohistochemical analysis characterized the expression profiles of MMP-2, MMP-9, COX-2, and RANKL/RANK/OPG and determined the presence of IL-1β, IL-10 and TNF-α, myeloperoxidase (MPO), malonaldehyde (MDA) and, glutathione (GSH). MPO activity in the group with periodontal disease was significantly increased compared to the control group (p<0.05). Rats treated with 10 mg/kg Carvedilol presented with significantly reduced MPO and MDA concentrations (p<0.05) in addition to presenting with reduced levels of the pro-inflammatory cytokines IL-1 β and TNF-α (p<0.05). IL-10 levels in Carvedilol-treated rats remained unaltered. Immunohistochemical analysis demonstrated reduced expression of MMP-2, MMP-9, RANK, RANKL, COX-2, and OPG in rats treated with 10 mg/kg Carvedilol. This study demonstrated that Carvedilol affected bone formation/destruction and anti-inflammatory activity in a rat model of periodontitis. Public Library of Science 2013-07-03 /pmc/articles/PMC3700994/ /pubmed/23843954 http://dx.doi.org/10.1371/journal.pone.0066391 Text en © 2013 Araújo Júnior et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author de Araújo Júnior, Raimundo Fernandes
Souza, Tatiana Oliveira
de Medeiros, Caroline Addison Xavier
de Souza, Lélia Batista
Freitas, Maria de Lourdes
de Lucena, Hévio Freitas
do Socorro Costa Feitosa Alves, Maria
de Araújo, Aurigena Antunes
spellingShingle de Araújo Júnior, Raimundo Fernandes
Souza, Tatiana Oliveira
de Medeiros, Caroline Addison Xavier
de Souza, Lélia Batista
Freitas, Maria de Lourdes
de Lucena, Hévio Freitas
do Socorro Costa Feitosa Alves, Maria
de Araújo, Aurigena Antunes
Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis
author_facet de Araújo Júnior, Raimundo Fernandes
Souza, Tatiana Oliveira
de Medeiros, Caroline Addison Xavier
de Souza, Lélia Batista
Freitas, Maria de Lourdes
de Lucena, Hévio Freitas
do Socorro Costa Feitosa Alves, Maria
de Araújo, Aurigena Antunes
author_sort de Araújo Júnior, Raimundo Fernandes
title Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis
title_short Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis
title_full Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis
title_fullStr Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis
title_full_unstemmed Carvedilol Decrease IL-1β and TNF-α, Inhibits MMP-2, MMP-9, COX-2, and RANKL Expression, and Up-Regulates OPG in a Rat Model of Periodontitis
title_sort carvedilol decrease il-1β and tnf-α, inhibits mmp-2, mmp-9, cox-2, and rankl expression, and up-regulates opg in a rat model of periodontitis
description Periodontal diseases are initiated primarily by Gram-negative, tooth-associated microbial biofilms that elicit a host response that causes osseous and soft tissue destruction. Carvedilol is a β-blocker used as a multifunctional neurohormonal antagonist that has been shown to act not only as an anti-oxidant but also as an anti-inflammatory drug. This study evaluated whether Carvedilol exerted a protective role against ligature-induced periodontitis in a rat model and defined how Carvedilol affected metalloproteinases and RANKL/RANK/OPG expression in the context of bone remodeling. Rats were randomly divided into 5 groups (n = 10/group): (1) non-ligated (NL), (2) ligature-only (LO), and (3) ligature plus Carvedilol (1, 5 or 10 mg/kg daily for 10 days). Periodontal tissue was analyzed for histopathlogy and using immunohistochemical analysis characterized the expression profiles of MMP-2, MMP-9, COX-2, and RANKL/RANK/OPG and determined the presence of IL-1β, IL-10 and TNF-α, myeloperoxidase (MPO), malonaldehyde (MDA) and, glutathione (GSH). MPO activity in the group with periodontal disease was significantly increased compared to the control group (p<0.05). Rats treated with 10 mg/kg Carvedilol presented with significantly reduced MPO and MDA concentrations (p<0.05) in addition to presenting with reduced levels of the pro-inflammatory cytokines IL-1 β and TNF-α (p<0.05). IL-10 levels in Carvedilol-treated rats remained unaltered. Immunohistochemical analysis demonstrated reduced expression of MMP-2, MMP-9, RANK, RANKL, COX-2, and OPG in rats treated with 10 mg/kg Carvedilol. This study demonstrated that Carvedilol affected bone formation/destruction and anti-inflammatory activity in a rat model of periodontitis.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700994/
_version_ 1611991654675251200