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.

Plasmatic NT-proBNP concentrations in patients with coexistent periodontal disease and congestive heart failure: pilot studies

“…Therefore, it could be suggested that the elimination of chronic inflammation related to active inflammation processes taking place in the periodontium, might lead to further benefits in the form of improved endothelial function of blood vessels. The subject of this pilot study was to examine the reduction of chronic inflammation related to PD influence on the clinical course and prognosis of CHF, based on the assessment of plasma concentrations of the inflammatory and neurohormonal markers NT-proBNP and TNF-a [21][22][23][24][25][26][27][28][29].…”

Retraction: Polyphosphate-induced matrix metalloproteinase-3-mediated proliferation in rat dental pulp fibroblast-like cells is mediated by a Wnt5 signaling cascade

“…MMP-3 has been implicated in joint and soft tissue destruction associated with these conditions, where it participates in the inflammatory response (10)(11)(12)(13). Synthesis of MMP-3 is tightly controlled in vivo (12,14).…”

Retraction：Polyphosphate-induced matrix metalloproteinase-3-mediated differentiation in rat dental pulp fibroblast-like cells

“…MMP-3 has been implicated in the joint and soft-tissue destruction associated with these conditions, where it participates in the inflammatory response (10)(11)(12)(13)(14). MMP-3 synthesis is tightly controlled in vivo (13,15).…”