Preventive effects of melatonin on periodontal tissue destruction due to psychological stress in rats with experimentally induced periodontitis

Abstract Objective and Background Psychological stress is a potential modifiable environmental risk factor causally related to the exacerbation of periodontitis and other chronic inflammatory diseases. This animal study aimed to investigate comprehensively the preventive efficacy of systemic melatonin administration on the possible effects of restraint stress on the periodontal structures of rats with periodontitis. Methods Forty‐eight male Sprague Dawley rats were randomly divided into six groups: control, restraint stress (S), S‐melatonin (S‐Mel), experimental periodontitis (Ep), S‐Ep, and S‐Ep‐Mel. Periodontitis was induced by placing a 3.0 silk suture in a sub‐paramarginal position around the cervix of the right and left lower first molars of the rats and keeping the suture in place for 5 weeks. Restraint stress was applied simultaneously by ligation. Melatonin and carriers were administered to the control, S, Ep, and S‐Ep groups intraperitoneally (10 mg/body weight/day, 14 days) starting on day 21 following ligation and subjection to restraint stress. An open field test was performed on all groups on day 35 of the study. Periodontal bone loss was measured via histological sections. Histomorphometric and immunohistochemical (RANKL and OPG) evaluations were performed on right mandibular tissue samples and biochemical (TOS (total oxidant status), TAS (total antioxidant status), OSI (oxidative stress index), IL‐1β, IL‐10, and IL‐1β/IL‐10) evaluations were performed on left mandibular tissue samples. Results Melatonin significantly limited serum corticosterone elevation related to restraint stress ( p < .05). Restraint stress aggravated alveolar bone loss in rats with periodontitis, while systemic melatonin administration significantly reduced stress‐related periodontal bone loss. According to the biochemical analyses, melatonin significantly lowered IL‐1β/IL‐10, OSI (TOS/TAS), and RANKL/OPG rates, which were significantly elevated in the S‐Ep group. Conclusion Melatonin can significantly prevent the limited destructive effects of stress on periodontal tissues by suppressing RANKL‐related osteoclastogenesis and oxidative stress.