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Oxid Med Cell Longev. 2018 Dec 2;2018:9421019. doi: 10.1155/2018/9421019. eCollection 2018.

Enhanced Oxidative Damage and Nrf2 Downregulation Contribute to the Aggravation of Periodontitis by Diabetes Mellitus.

Li X1,2, Sun X2,3, Zhang X2,4, Mao Y1,4, Ji Y4, Shi L4, Cai W4, Wang P5, Wu G2, Gan X6, Huang S1,2,4.

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Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam 1081 LA, Netherlands.
Department of Periodontology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Department of Periodontology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.


Diabetes mellitus is a well-recognized risk factor for periodontitis. The goal of the present study was to elucidate whether oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) participate in the aggravation of periodontitis by diabetes. For this purpose, we assigned Wistar rats to control, periodontitis, diabetes, and diabetic periodontitis groups. Two weeks after induction of diabetes by streptozotocin, periodontitis was induced by ligation. Two weeks later, periodontal tissues and blood were harvested and analyzed by stereomicroscopy, immunohistochemistry, and real-time polymerase chain reaction. We found that ligation induced more severe bone loss and periodontal cell apoptosis in diabetic rats than in normal rats (p < 0.05). Compared with the control group, periodontitis significantly enhanced local oxidative damage (elevated expression of 3-nitrotyrosine, 4-hydroxy-2-nonenal, and 8-hydroxy-deoxyguanosine), whereas diabetes significantly increased systemic oxidative damage and suppressed antioxidant capacity (increased malondialdehyde expression and decreased superoxide dismutase activity) (p < 0.05). Simultaneous periodontitis and diabetes synergistically aggravated both local and systemic oxidative damage (p < 0.05); this finding was strongly correlated with the more severe periodontal destruction in diabetic periodontitis. Furthermore, gene and protein expression of Nrf2 was significantly downregulated in diabetic periodontitis (p < 0.05). Multiple regression analysis indicated that the reduced Nrf2 expression was strongly correlated with the aggravated periodontal destruction and oxidative damage in diabetic periodontitis. We conclude that enhanced local and systemic oxidative damage and Nrf2 downregulation contribute to the development and progression of diabetic periodontitis.

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