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

• Published in: PloS one 2013-07, Vol.8 (7), p.e66391-e66391
• 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: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; Antioxidants; Atherosclerosis; Biofilms; Biology; Bone growth; Bone remodeling; Bone remodelling; Carbazoles - administration & dosage; Carbazoles - pharmacology; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Dental research; Destruction; Disease control; Disease Models, Animal; Enzymes; Gelatinase A; Gelatinase B; Glutathione; Gum disease; Heart failure; Inflammation; Interleukin 1; Interleukin 10; Interleukin-1beta - metabolism; Male; Malondialdehyde; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medicine; Microorganisms; Microscopy; Morphology; Neutrophils; Osteogenesis; Osteoprotegerin; Osteoprotegerin - metabolism; Oxidative Stress; Periodontal disease; Periodontal diseases; Periodontitis; Periodontitis - genetics; Periodontitis - metabolism; Periodontitis - pathology; Peroxidase; Propanolamines - administration & dosage; Propanolamines - pharmacology; Public health; RANK Ligand - metabolism; Rats; Rodents; Teeth; TRANCE protein; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066391

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