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

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-1ß, IL-10, and IL-1ß/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-1ß/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.

Melatonin supports nonsurgical periodontal treatment in patients with Type 2 diabetes mellitus and periodontitis: A randomized clinical trial.

BACKGROUND: Diabetes mellitus (DM)-associated hyperinflammatory host response significantly provokes periodontal tissue destruction. In this context, the support of nonsurgical periodontal therapy in diabetics with host modulation agents is a current field of study. This clinical study aims to investigate the clinical efficacy of melatonin supplementation and discuss its possible biological mechanisms in nonsurgical periodontal treatment in patients with DM and periodontitis through some fundamental markers. METHODS: In this randomized controlled and single-blind study, 27 of 55 diabetic patients with periodontitis (stage III/IV and grade C) underwent full-mouth scaling and root planing (fmSRP) alone and 28 patients underwent melatonin administration (6 mg daily, 30 days) in addition to fmSRP (full-mouth scaling and root planing plus melatonin, fmSRP-mel). The potential therapeutic contribution of melatonin was evaluated clinically and biochemically (gingival crevicular fluid RANKL, OPG, MMP-8, and serum IL-1ß levels) at 3rd and 6th months. RESULTS: Melatonin (tablet, 6 mg daily, 30 days) did not cause any local or systemic side effects. fmSRP alone resulted in significant reduction in serum IL-1ß levels, pocket depths, gingival inflammation, and gingival crevicular fluid RANKL and MMP-8 levels (p < 0.05). Moreover, melatonin supplementation resulted in a more significant decrease in bleeding and pocket depth scores at probing, especially at 3 months (p < 0.05). Furthermore, RANKL and MMP-8 levels were significantly lower at 3 months and IL-1ß levels at 6 months compared to the control group (p < 0.05). However, OPG levels were not affected significantly by the treatments (p > 0.05). CONCLUSION: Melatonin, as a host modulation agent, significantly increases the clinical efficacy of fmSRP. The reduction in periodontal inflammation and pocket depths may be a result of marked suppression of RANKL-associated osteoclastogenesis and extracellular matrix damage by melatonin.

The effects of vitamin D deficiency on mandibular bone structure: a retrospective radiological study.

OBJECTIVE: The aim of the study was to evaluate the effects of vitamin D deficiency on the mandibular bone structure by fractal analysis and panoramic morphometric indices. METHODS: Ninety participants were divided into three groups as 30 individuals with severe vitamin D deficiency, 30 individuals with vitamin D deficiency, and 30 individuals with vitamin D sufficiency. Fractal dimension analysis (FD), panoramic mandibular index (PMI), mandibular cortical index (MCI), and mandibular cortical thickness measurement (CTM) were evaluated on panoramic radiographs. RESULTS: FD values of the patients with vitamin D deficiency were found to be statistically lower than the patients with vitamin D sufficiency (p < 0.05). FD value of supracortical area above the angulus mandible (FD2) in patients with severe vitamin D deficiency was significantly lower than FD values (p = 0.002). There was no statistically significant difference between the groups in the CTM (p > 0.05). PMI was significantly lower in patients with severe vitamin D deficiency (p < 0.001). There was a significant difference in MCI values between the groups (p < 0.05). CONCLUSION: Vitamin D deficiency causes a decrease in bone mineral density in the mandible, and an increase in alveolar porosity. FD analysis and radiomorphometric indices in panoramic radiographs can be used to assess osteoporotic changes in patients with vitamin D deficiency.

Effects of hyperlipidemia on trabecular and cortical structures of the mandible.

OBJECTIVES: To evaluate the mandibular bone structure of patients with hyperlipidemia by fractal dimension (FD) analysis and panoramic radiomorphometric indices including mandibular cortical thickness measurement, panoramic mandibular index (PMI), mandibular cortical index (MCI) and to compare with the healthy group. METHODS: In total, 60 panoramic radiographs were included, including panoramic radiographs of 30 individuals with hyperlipidemia and 30 individuals with systemically healthy. FD analysis in the mandibular condyle, angle of the mandible, the distal side of the second premolar and anterior to mental foramen, PMI, MCI, and mandibular cortical thickness measurements were evaluated on radiographs. Independent samples t-test was used for differences between healthy and hyperlipidemia groups with regard to age and PMI. Repeated measurement of variance with one within and one between factors in the comparison of four regions and two groups in terms of FD and cortical thickness measurements. Following this analysis, significant differences were detected by post-hoc Sidak test. Fisher-Freeman-Halton analysis was applied to determine the relationship between categorical variables. RESULTS: FD values of the hyperlipidemic patients were found to be lower than the healthy group. Between the hyperlipidemic and healthy groups, there was a difference in the angle of the mandible FD values (p = 0.020). There were no differences in the cortical thickness measurements and PMI between the groups (p > 0.05). There was a difference in MCI values between the groups (p < 0.05). CONCLUSION: The trabecular structure of the angle of the mandible and the cortical bone structure of the mandible were found to be negatively affected by hyperlipidemia.

Influences of periodontitis on hippocampal inflammation, oxidative stress, and apoptosis in rats.

BACKGROUND AND AIM: The hippocampus, which has a central role in cognitive and behavioral activities, is one of the most sensitive parts of the brain to systemic inflammatory diseases. This animal study aims to comprehensively investigate the possible inflammatory, oxidative, and apoptotic effects of periodontitis on the hippocampus. METHODS: Sixteen male Sprague-Dawley rats were randomly assigned to two groups: control and experimental periodontitis (Ep). In the Ep group, periodontitis was induced by placing 3.0 sutures sub-paramarginally around the necks of right and left mandibular first molars and maintaining the ligatures in place for 5 weeks. Following the euthanasia, mandibula and hippocampus samples were collected bilaterally. Alveolar bone loss was measured histomorphometrically and radiologically on the right and left mandibles. On the right hippocampal sections histological (Caspase-3, TNF-α, and 8-OHdG) and the left hippocampal sections, biochemical (IL-1ß, Aß1-42 , MDA, GSH, and TAS levels) evaluations were performed. RESULTS: Histopathological changes associated with periodontitis were limited (p > .05). A slight increase in caspase-3 positive neuron density in EP rats showed that apoptotic changes were also limited (p > .05). 8-OHdG activity, on the other hand, was significantly higher compared to controls (p < .05). In biochemical analysis, there was a significant increase in IL-1ß levels and oxidative membrane damage (MDA) (p < .05) whereas Aß1-42 and antioxidant marker (GSH and TAS) levels were slightly increased (p > .05). CONCLUSION: Periodontitis causes marked increases in IL-1ß levels and oxidative stress in the hippocampus, but limited degenerative and apoptotic changes.

Melatonin ameliorates periodontitis-related inflammatory stress at cardiac left ventricular tissues in rats.

BACKGROUND: The aim of this experimental rat study was to investigate the potential inflammatory effects of periodontitis on cardiac left ventricular tissue and the therapeutic activity of melatonin on these effects. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Experimental periodontitis was induced by placing and maintaining 3.0 silk ligatures at a peri marginal position on the left and right mandibular first molars for 5 weeks. Afterward, following the removal of ligatures, melatonin (10 mg/body weight) to Ep-Mel group, and vehicle (saline) to Ep and control groups were administered intraperitoneally for 14 days. On the first day of the eighth week, mandibular and cardiac left ventricular tissue samples were obtained following the euthanasia of the rats in all groups. Alveolar bone loss measurements were made on histological and microcomputed tomographic slices. Cardiac tissue levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), matrix metalloproteinase-9 (MMP-9), and cardiac Troponin-T (cTnT) were evaluated by appropriate biochemical methods. RESULTS: Measurements made on the histological and microcomputed tomographic slices showed that melatonin significantly limits the ligature-induced periodontal tissue destruction (P <0.01). In addition, melatonin was detected to cause a significant decrease of MDA, MMP-9, and cTnT levels which were found to be significantly higher on rats with Ep (P <0.05) while having no significant effect on antioxidant levels (GSH, SOD, and CAT) (P >0.05). CONCLUSION: Melatonin might be regarded as an important supportive therapeutic agent to reduce the early degenerative changes and possible hypertrophic remodeling at cardiac left ventricular tissues provoked by periodontitis-related bacteria and/or periodontal inflammation.

Influences of Fucoxanthin on Alveolar Bone Resorption in Induced Periodontitis in Rat Molars.

The aim of this study was to evaluate the effects of systemic fucoxanthin treatment on alveolar bone resorption in rats with periodontitis. Thirty rats were divided into control, experimental periodontitis (EP), and experimental periodontitis-fucoxanthin (EP-FUCO) groups. Periodontitis was induced by ligature for four weeks. After removal of the ligature, the rats in the EP-FUCO group were treated with a single dose of fucoxanthin (200 mg/kg bw) per day for 28 consecutive days. At the end of the study, all of the rats were euthanized and intracardiac blood and mandible tissue samples were obtained for biochemical, immunohistochemical, and histometric analyses. Fucoxanthin treatment resulted in a slight decrease in tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels and a significant decrease in oxidative stress index. It was observed that fucoxanthin caused a significant reduction in receptor activator of nuclear factor kappa-ß ligand (RANKL) levels and a statistically non-significant elevation in osteoprotegerin and bone-alkaline phosphatase levels. There were no significant differences in alveolar bone loss levels between the EP and EP-FUCO groups. This experimental study revealed that fucoxanthin provides a limited reduction in alveolar bone resorption in rats with periodontitis. One of the mechanisms underlying the mentioned limited effect might be related to the ability of fucoxanthin to inhibit oxidative stress-related RANKL-mediated osteoclastogenesis.

Effects of Melatonin on Oxidative Stress Index and Alveolar Bone Loss in Diabetic Rats With Periodontitis.

BACKGROUND: The aim of this study is to evaluate the effects of systemic melatonin treatment on serum oxidative stress index (OSI) and alveolar bone loss (ABL) in rats with diabetes mellitus (DM) and periodontitis. METHODS: Seventy Sprague Dawley rats were divided into control, experimentally induced periodontitis (EP), DM, EP-DM, EP and melatonin treatment (EP-MEL), DM and melatonin treatment (DMMEL), and EP-DM-MEL groups. DM was induced by alloxan, after which periodontitis was induced by ligature for 4 weeks. After removal of the ligature, the rats in the melatonin groups (EP-MEL, DM-MEL, and EP-DM-MEL) were treated with a single dose of melatonin (10 mg/body weight) every day for 14 consecutive days. At the end of the study, all of the rats were euthanized, and intracardiac blood samples and mandible tissues were obtained for biochemical and histologic analyses. Serum levels of total oxidant status/total antioxidant status and OSI were measured. In addition, neutrophil and osteoclast densities and myeloperoxidase activities were determined in gingival tissue homogenates, and ABL was evaluated with histometric measurements. RESULTS: Melatonin treatment significantly reduced fasting plasma glucose levels in the rats with DM. In addition, reduced OSI and ABL levels were detected in the EP-MEL and DM-MEL groups; the reductions in the EP-DM-MEL group were found to be more prominent. Melatonin also significantly decreased the increased myeloperoxidase activities and osteoclast and neutrophil densities in the EP, DM, and EP-DM groups. CONCLUSION: It is revealed in this experimental study that melatonin significantly inhibited hyperglycemia-induced oxidative stress and ABL through antiDM and antioxidant effects in rats with DM and periodontitis.