Blood Oxidative Stress Modulates Alveolar Bone Loss in Chronically Stressed Rats

Abstract

We aimed to investigate the effects of chronic stress (CS) on experimental periodontitis (EP) in rats. For this, 28 Wistar rats were divided into four groups: control, ligature-induced experimental periodontitis (EP), chronic stress (CS; by physical restraint model) and CS+EP (association of chronic stress and ligature-induced periodontitis). The experimental period lasted 30 days, including exposure to CS every day and ligature was performed on the 15th experimental day. After 30 days, the animals were submitted to the behavioral test of the elevated plus maze (EPM). Next, rats were euthanized for blood and mandible collection in order to evaluate the oxidative biochemistry (by nitric oxide (NO), reduced-glutathione activity (GSH), and thiobarbituric acid reactive substance levels (TBARS)) and alveolar bone characterization (by morphometric, micro-CT, and immunohistochemistry), respectively. The behavioral parameters evaluated in EPM indicated higher anxiogenic activity in the CS and CS+EP, groups, which is a behavioral reflex of CS. The results showed that CS was able to change the blood oxidative biochemistry in CS and CS+EP groups, decrease GSH activity in the blood, and increase the NO and TBARS concentrations. Thus, CS induces oxidative blood imbalance, which can potentialize or generate morphological, structural, and metabolic damages to the alveolar bone.

Aggravating Effects of Psychological Stress on Ligature-Induced Periodontitis via the Involvement of Local Oxidative Damage and NF-κB Activation

“…Accompanying the results of increased CORT and ACTH contents as well as decreased sucrose preference, we confirmed that the CUMS protocol in this study induced a depression-like state in the PS and EP+PS animals. In addition, because it causes plaque retention, the method used in this study of tying a ligature around the teeth is widely used to establish periodontal disease in animals [ 8 , 11 , 12 , 14 ]. Although we did not find any changes in alveolar bone loss, attachment loss, or cytokine protein expression in the gingiva of stressed rats, we confirmed that multiple stressors worsened these parameters in rats with silk ligature-induced periodontitis.…”

“…Therefore, it is reasonable to suppose that hypoxia occurs in the periodontium [ 36 ] when rats undergo long-term stress. Lopes Castro et al [ 12 ] have reported oxidative imbalance in a blood sample and consider that the disequilibrium of oxidation and antioxidation could potentialize or generate alveolar bone lesions in chronically stressed rats. In the current study, we first observed that the local anomalous redox trend was worse in the inflamed gingiva following psychological stress.…”

“…The association between psychological stress and periodontitis has been largely demonstrated recently [ 6 , 7 , 8 ] and has been identified as a potential risk factor for periodontal disease in some observational studies [ 9 , 10 ]. Also, researchers established a conditioned fear stress model and physical restraint model in rats to induce psychological stress and confirmed that stress is associated with the progression of alveolar bone loss with altered RANK and RANKL expressions as well as quality of alveolar bone [ 11 , 12 ]. Some studies even indicated that psychosocial stress has a greater influence than pathogenic bacteria on the severity of periodontal inflammation [ 13 ].…”

“…Redox homeostasis is disturbed under anaerobic conditions, resulting in an imbalance between the oxidant and antioxidant defence systems. This leads to oxidative stress, which has been demonstrated to damage periodontal health [ 12 , 19 , 20 ]. Nuclear factor kappa B (NF- κ B) is a transcription factor with numerous biological functions, including regulating the expression of various proinflammatory factors involved in inflammation [ 21 ].…”

Molecular Mechanisms of Periodontal Disease

“…Based on the emerging evidence, in their review article, Aquino-Martinez et al proposed a new scientific model that senescent cells, which receive oxidative stress and subsequent DNA damage, may aggravate the innate immune reaction against pathogens [ 12 ]. Lopes et al indicated that chronic stress-induced blood oxidative stress exacerbates periodontal bone resorption using the rat physical restraint model [ 13 ].…”