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

Abstract

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.

Oxidative stress‐related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: A systematic review and meta‐analysis

“…In addition, the CP patients had significantly higher salivary MDA level than the healthy controls. This might be associated with increased percentage of GCF in saliva in periodontitis (Gawron‐Skarbek & Chrzczanowicz, ) and suggests that salivary MDA level could also be used as an indicator of periodontal damage by ROS (Li et al., ).…”

The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway

“…DM group: rats were intraperitoneally injected with 35 mg/kg streptozotocin (STZ; dissolved in 1% sodium citrate buffer, pH = 4.5; Sigma‐Aldrich) to induce type 2 DM. Three days following STZ administration, rats with fasting blood glucose concentrations ≥16.7 mmol/L and decreased insulin sensitivity were selected as the STZ‐induced DM group CPDM group: 1 month after confirmation of diabetes, periodontitis was induced for another 1 month. CPDM treatment groups: rats were administered with BCI diluted in PBS by oral gavage for 1 month at three dose groups (50, 100, or 200 mg/kg/d). …”

Possible Involvement of Vitamin C in Periodontal Disease-Diabetes Mellitus Association

“…In a study with murine models with diabetes, Li et al [58] found that simultaneous periodontitis and DM synergistically aggravated both local and systemic oxidative lesions, being correlated with more severe periodontal destruction in diabetic periodontitis.…”