Direct-Acting Oral Anticoagulant/Vitamin K Antagonists: Do They Affect the Trabecular and Cortical Structure of the Mandible?

BACKGROUND: This study aimed to evaluate the mandibular bone structure of patients using oral anticoagulants (OACs) vitamin K antagonist drugs (warfarin) and other OACs including direct oral anticoagulants [(DOACs) apixaban, rivaroxaban, dabigatran, edoxaban]. Analyses were based upon the fractal dimension (FD), the panoramic mandibular index (PMI) and the Klemetti index (KI), which is also known as the mandibular cortical index (MCI). METHODOLOGY: Ninety participants were divided into three groups: group 1: 30 systemically healthy individuals who had not used any anticoagulants before, group 2: 30 individuals using warfarin, and group 3: 30 individuals using DOACs. FD was used to analyze trabecular bone architecture in the condyle, angle, and two sites in the alveolar bone. PMI was used to evaluate the quantity of cortical bone and KI was used to evaluate the cortical bone quality. RESULTS: There was no difference between the groups regarding FD analysis and KI; however, a difference was found between groups 1, 2, and 3 in the PMI (P≤ 0.001). The PMI in group 1 was higher than in groups 2 and 3. CONCLUSION: Mandibular radiomorphometric indices can be used on panoramic radiographs to evaluate the quantity of mandibular cortical bone in patients using oral anticoagulants.

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.

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.

Periodontitis exacerbates the renal degenerative effects of obesity in rats.

BACKGROUND/OBJECTIVES: Obesity and periodontitis are systemic subclinical inflammatory diseases with established negative renal effects. The aim of this animal study was to thoroughly investigate the possible effects of these two diseases on renal structure and function. METHODS: Thirty-two male Sprague Dawley rats were divided into four groups: control (C), obesity (Ob), experimental periodontitis (Ep), and Ob + Ep. The first 16 weeks of the experiment were aimed for the induction of obesity and the last 5 weeks for the induction of periodontitis. Throughout the experimental period, the C and Ep groups were fed standard rat chow, while the Ob groups (Ob and Ob + Ep) were fed high-fat rat chow. Right after the establishment of obesity, periodontal tissue destruction was achieved by placing 3.0 silk sutures in sub-paramarginal position around the cervices of mandibular right-left first molar teeth and preserving them for 5 weeks. On the last day of the 22nd week, following blood collection, all rats were euthanized, and kidneys and mandibles were collected. Alveolar bone loss was measured on microcomputed tomographic slices. Histopathological evaluations (light microscopy, semi-quantitative analysis of renal corpuscle area, and immunohistochemical analysis of caspase-3 activity) were done on right kidneys and biochemical evaluations (malonyl-aldehyde [MDA], glutathione [GSH], total oxidant status [TOS], total antioxidant status [TAS], oxidative stress [OSI], tumor necrosis factor-α [TNF-α], interleukin-1ß [IL-1ß], matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D [CtD] levels) were done on left kidneys. Renal functional status was evaluated with levels of serum creatinine, urea, and cystatin C. RESULTS: Periodontal bone loss was significantly higher in the Ep and Ob + Ep groups, compared with the C and Ob groups (p < .05). All parameters except TAS and GSH were highest in the Ob + Ep group, and the differences were statistically significant compared with the control group (p < .05). Although the mean TAS and GSH levels were lower in the Ob + Ep group than the other groups, the differences were not statistically significant (p > .05). While the atypical glomeruli score was significantly higher in the Ob + Ep group than in all other groups (p < .05), the acute tubular necrosis and histopathological scores were significantly different only compared with the control group (p < .05). CONCLUSION: This experimental study showed that the negative effects of the co-existence of periodontitis and obesity on inflammatory stress and apoptotic changes in the kidneys together with the functional parameters were significantly more severe, compared with the presence of one of these diseases alone. TNF-α could have a central role in the periodontitis and obesity-related structural and functional renal changes.

Melatonin improves periodontitis-induced kidney damage by decreasing inflammatory stress and apoptosis in rats.

BACKGROUND: Two main aims of this animal study were to inspect the possible effects of periodontitis on the structure and functions of the kidneys and the therapeutic effectiveness of melatonin. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Periodontitis was induced by placing 3.0-silk sutures sub-paramarginally around the cervix of right-left mandibular first molars and maintaining the sutures for 5 weeks. Then melatonin (10 mg/kg body weight/day, 14 days), and the vehicle was administered intraperitonally. Mandibular and kidney tissue samples were obtained following the euthanasia. Periodontal bone loss was measured via histological and microcomputed tomographic slices. On right kidney histopathological and immunohistochemical, and on the left kidney biochemical (malonyl-aldehyde [MDA], glutathione, oxidative stress [OSI], tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D levels) evaluations were performed. Renal functional status was analyzed by levels of serum creatinine, urea, cystatin-C, and urea creatinine. RESULTS: Melatonin significantly restricted ligature-induced periodontal bone loss (P <0 .01) and suppressed the levels of proinflammatory cytokines (TNF-α and IL-1ß), oxidative stress (MDA and OSI), and proteases (MMP-8, MMP-9, and CtD) that was significantly higher in the kidneys of the rats with periodontitis (P <0.05). In addition, periodontitis-related histological damages and apoptotic activity were also significantly lower in the Ep-Mel group (P <0.05). However, the markers of renal function of the Ep group were detected slightly impaired in comparison with the control group (P >0.05); and the therapeutic activity of melatonin was limited (P >0.05). CONCLUSION: Melatonin restricts the periodontitis-induced inflammatory stress, apoptosis, and structural but not functional impairments.