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.
abstract: 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.
authors.affiliation: Post Graduation Program in Functional and Structural Biology/Post Graduation Program Health Science/Department of Morphology, UFRN, Natal, Rio Grande do Norte, Brazil. aurigena@ufrnet.br
authors.forename: Raimundo Fernandes
authors.initials: RF
authors.lastname: de Araújo Júnior
authors.forename: Tatiana Oliveira
authors.initials: TO
authors.lastname: Souza
authors.forename: Caroline Addison Xavier
authors.initials: CA
authors.lastname: de Medeiros
authors.forename: Lélia Batista
authors.initials: LB
authors.lastname: de Souza
authors.forename: Maria de Lourdes
authors.initials: Mde L
authors.lastname: Freitas
authors.forename: Hévio Freitas
authors.initials: HF
authors.lastname: de Lucena
authors.forename: Maria
authors.initials: M
authors.lastname: do Socorro Costa Feitosa Alves
authors.forename: Aurigena Antunes
authors.initials: AA
authors.lastname: de Araújo
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism*; D018384:Oxidative Stress; D010518:Periodontitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D002227:Carbazoles; D053583:Interleukin-1beta; D053244:Osteoprotegerin; D011412:Propanolamines; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D000077261:Carvedilol; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9