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

Abstract

This study aimed to determine the role of resveratrol (RESV) on the progression of experimental periodontitis (EP) in ovariectomy rats (OVT). 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. 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 (10mg/kg), and ZLD (0.1mg/kg) was carried out for a period 42days prior to initiation of EP, and then for another 28days 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. 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). It can be concluded that resveratrol modulated alveolar bone loss during experimental periodontitis progression in estrogen-deficient rats by downregulating NADPH oxidase levels.