Investigation of the effects of systemic melatonin administration on periodontitis-associated nonalcoholic fatty liver disease in experimental periodontitis rats

Aim: The aim was to investigate the possible effects of periodontitis on liver tissue and the therapeutic efficacy of systemically administered melatonin in non-alcoholic liver disease patients with experimental periodontitis. Material and Methods: 48 female Sprague-Dawley rats were randomly divided into six groups: control, Non-Alcoholic Fatty Liver (NAFLD), experimental periodontitis (Ep), NAFLD + Ep, NAFLD + Melatonin (Mel), and NAFLD + Ep + Mel. A NAFLD model was established in rats fed a high-fat, high-cholesterol (HFHC) diet for 9 weeks. Periodontitis was then induced by placing 4.0 silk suture in the subparamarginal position across the necks of the right and left mandibular first molars and maintaining the suture in place for 5 weeks. Following the induction of periodontitis, melatonin and vehicle (Control and Ep groups) were administered intraperitoneally (10 mg/body weight/day, 14 days). Tissue samples from the rats' lower jaw and liver were collected. Alveolar bone loss was measured using microcomputed tomographic sections. Immunohistochemical (RANKL, OPG, TGF-β) on the mandible, histopathological, immunohistochemical (caspase-3), and biochemical (MDA, GSH, OSI, TNF-α, IL-1β, IL-6, leptin, adiponectin, total cholesterol, HDL, ALT, AST) were evaluated on the liver. Results: According to our findings, the highest body weight was found in the NAFLD+Dp+Mel group, and the highest liver weight was found in the NAFLD+Dp group (p<0.05). Alveolar bone loss was greatest in the NAFLD+Dp group, and melatonin administration reduced this loss. Histopathological findings revealed significant necrosis, inflammation, and vascular congestion in the Dp, NAFLD, and NAFLD+Dp groups, while melatonin administration improved these findings. The highest LHDS scores were in the NAFLD+Dp group. Caspase-3-positive hepatocytes increased in the NAFLD, Dp, and NAFLD+Dp groups, but decreased following melatonin administration. RANKL, OPG, and TGF-β expression in alveolar bone increased in the NAFLD+Dp group and decreased following melatonin administration. Biochemical analyses revealed that TNF-α levels were significantly higher in the NAFLD, Dp, and NAFLD+Dp groups compared to the other groups. IL-6 levels were significantly lower in the control and NAFLD+Dp+Mel groups compared to the other groups. AST levels were higher in the NAFLD and NAFLD+Dp groups compared to the other groups and significantly decreased with melatonin administration. Conclusion: Melatonin can effectively limit disorders such as inflammatory stress and apoptosis in periodontitis-associated non-alcoholic fatty liver disease.