Effect of resveratrol on the progression of experimental periodontitis in an ovariectomized rat model of osteoporosis: Morphometric, immune-enzymatic, and gene expression analysis.

OBJECTIVE: This study aimed to determine the role of resveratrol (RESV) on the progression of experimental periodontitis (EP) in ovariectomy rats (OVT). BACKGROUND: Estrogen deficiency is the main cause of osteoporosis and is related to higher periodontal attachment loss and reduction of alveolar bone. Zoledronate (ZLD) is an antiresorptive drug used to control osteoporosis but can lead to osteonecrosis of the jaw. RESV, a natural product, can reduce bone loss and control and prevent osteoporosis. Thus, this study aimed at investigating the effect of RESV on the progression of EP in estrogen-deficient rats. MATERIAL AND METHODS: The animals were subjected to the OVT or sham surgery to induce estrogen-deficiency and then were divided into the groups: OVT + RESV (n: 10); OVT + PLAC (n: 10): OVT + placebo; OVT + ZLD +PLA (n: 10); OVT + RESV +ZLD (n: 10): OVT + RESV and ZLD; SHAM (n: 10): non-ovariectomized animals + placebo. To induce estrogen deficiency, the rats were subjected to ovariectomy. Experimental periodontitis was induced by the placement of a ligature at the second maxillary molars. Daily administration of the placebo solution, resveratrol (10 mg/kg), and ZLD (0.1 mg/kg) was carried out for a period 42 days prior to initiation of EP, and then for another 28 days following ligature placement. After euthanasia, the specimens were processed for micro-CT and morphometric analysis of bone loss (linear measurement), and the gingival tissue surrounding the maxillary second molar was collected for the quantification of inflammatory markers using Luminex/MAGPix, of oxidative stress markers using ELISA assay, and gene expression analysis of bone markers, by real-time PCR. RESULTS: Morphometric and micro-CT analysis showed higher bone loss and lower bone density, respectively, in OVT + PLAC when compared to the other groups (P < .05). ZLD treated groups had lower alveolar bone loss, as well as, higher density and percentage of bone volume, when compared to OVT + RESV and SHAM + PLAC groups (P < .05). IL-4 levels were significantly lower in the OVT + PLAC group versus OVT + ZLD +RESV and SHAM + PLAC (P < .05). NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) levels were significantly lower OVT + RESV group when compared to OVT + PLAC (P < .05). OPG mRNA levels were lower in OVT + PLAC compared with the SHAM + PLAC group (P < .05). CONCLUSION: It can be concluded that resveratrol modulated alveolar bone loss during experimental periodontitis progression in estrogen-deficient rats by downregulating NADPH oxidase levels.

Resveratrol and insulin association reduced alveolar bone loss and produced an antioxidant effect in diabetic rats.

BACKGROUND: The present investigation studied the effects of systemic administration of resveratrol (RSV) on the development of experimental periodontitis (EP) and on the release of markers of inflammation, bone metabolism, and oxidative stress in diabetic rats. METHODS: Seventy-five male rats were divided into five groups: DM+PLAC: Diabetes Mellitus + placebo solution; DM+INS: DM + insulin therapy; DM+RSV: DM + RSV; DM+RSV+INS: DM + RSV and insulin; NDM: non-diabetic. Streptozotocin was used to induce DM and EP was induced by the placement of a ligature at the fist mandibular and the second maxillary molars. Euthanasia occurred 30 days after the initiation of the study and mandible specimens were subjected for morphometric analysis of bone level. Gingival tissues from mandibular molars were collected for quantification of inflammatory and oxidative stress markers by multiplex assay system and ELISA assay, respectively. Maxillary gingival tissues were processed for real-time polymerase chain reaction (real-time PCR) assessment of markers of bone metabolism and oxidative stress. RESULTS: Morphometric analysis revealed greater bone loss in DM+PLAC and DM+INS in comparison to the other treatments (P < 0.05). RSV used in conjunction with INS reduced the levels of interleukin (IL)-1ß, IL-6, IL-17, interferon-gamma (IFN-γ) and superoxide dismutase 1 (SOD) (P < 0.05). RSV alone reduced nicotinamide adenine dinucleotide phosphatase oxidase (NADPH oxidase) levels, in comparison to DM+INS and DM+RSV+INS (P < 0.05). All treatments upregulated mRNA levels for osteoprotegerin (OPG) in comparison to PLAC (P < 0.05). Sirtuin 1 (SIRT) mRNA levels were lower in PLAC when compared to DM+RSV, DM+RSV+INS and NDM (P < 0.05). CONCLUSION: RSV reduced the progression of EP and the levels of NADPH oxidase. Co-treatment with RSV and insulin reduced the levels of pro-inflammatory factors (either proteins or mRNA) and increased the levels of SOD. The data also demonstrated that treatment with RSV and INS alone or in combination had beneficial effects on bone loss.