title: Resveratrol improves oxidative stress and prevents the progression of periodontitis via the activation of the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in a rat periodontitis model.
abstract: Oxidative stress is a key factor regulating the systemic pathophysiological effects associated with periodontitis. Resveratrol is a phytochemical with antioxidant and anti-inflammatory properties that can reduce oxidative stress and inflammation. We hypothesized that resveratrol may prevent the progression of periodontitis and reduce systemic oxidative stress through the activation of the sirtuin 1 (Sirt1)/AMP-activated protein kinase (AMPK) and the nuclear factor E2-related factor 2 (Nrf2)/antioxidant defense pathways. Three groups of male Wistar rats (periodontitis treated with melinjo resveratrol, periodontitis without resveratrol, and control rats with no periodontitis or resveratrol treatment) were examined. A ligature was placed around the maxillary molars for 3 weeks to induce periodontitis, and the rats were then given drinking water with or without melinjo resveratrol. In rats with periodontitis, ligature placement induced alveolar bone resorption, quantified using three-dimensional images taken by micro-CT, and increased proinflammatory cytokine levels in gingival tissue. Melinjo resveratrol intake relieved alveolar bone resorption and activated the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in inflamed gingival tissues. Further, melinjo resveratrol improved the systemic levels of 8-hydroxydeoxyguanosine, dityrosine, nitric oxide metabolism, nitrotyrosine, and proinflammatory cytokines. We conclude that oral administration of melinjo resveratrol may prevent the progression of ligature-induced periodontitis and improve systemic oxidative and nitrosative stress.
authors.affiliation: Department of Preventive Dentistry and Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan. Electronic address: tamanaof@tokushima-u.ac.jp.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Tamaki
authors.affiliation: Department of Preventive Dentistry and Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Rita
authors.initials: R
authors.lastname: Cristina Orihuela-Campos
authors.affiliation: Department of Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Department of Preventive Dentistry and Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukui
authors.affiliation: Department of Periodontology and Endodontology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Preventive Dentistry and Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Hiro-O
authors.initials: HO
authors.lastname: Ito
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001862:Bone Resorption / Q000188:drug therapy; D016207:Cytokines / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D005881:Gingiva / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D010518:Periodontitis / Q000188:drug therapy / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D013267:Stilbenes; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; C007543:dityrosine; D055372:AMP-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D003849:Deoxyguanosine; D000077185:Resveratrol
keywords: AMPK; Cytokines; Free radicals; Nrf2; Oxidative stress; Periodontitis; Resveratrol; Sirt1