Vitale Marcelo, Corrêa Mônica Grazieli, Ervolino Edilson, Cirano Fabiano Ribeiro, Ribeiro Fernanda Vieira, Monteiro Mabelle Freitas, Casati Marcio Zaffalon, Pimentel Suzana Peres
Dental Research Division, School of Dentistry, Paulista University, São Paulo, Brazil.
Department of Basic Sciences, Dental School of Araçatuba, University Estadual Paulista, UNESP, Araçatuba, Brazil.
Oral Dis. 2024 Apr;30(3):1462-1474. doi: 10.1111/odi.14544. Epub 2023 Mar 13.
This study evaluated the effect of resveratrol (RES) on the prevention of medication-related osteonecrosis of the jaws (MRONJ) in ovariectomized (OVX) rats treated with zoledronate (ZOL). Fifty rats were distributed in five groups: SHAM (n = 10): non-ovariectomy + placebo; OVX (n = 10):ovariectomy + placebo; OVX + RES (n = 10):ovariectomy + resveratrol; OVX + ZOL (n = 10):ovariectomy + placebo + zoledronate; and OVX + RES + ZOL (n = 10):ovariectomy + resveratrol + zoledronate. The mandibles left sides were analyzed with micro-CT, histomorphometry, and immunohistochemistry. On the right side, bone markers gene expression was analyzed by qPCR. ZOL increased the percentage of necrotic bone and reduced the neo-formed bone compared to groups not receiving ZOL (p < 0.05). RES impacted the tissue healing pattern in OVX + ZOL + RES, reduced inflammatory cell infiltrate, and improved bone formation in the extraction site. Osteoblasts, alkaline phosphatase (ALP)-, and osteocalcin (OCN)-immunoreactive cells were lower in OVX-ZOL than in SHAM, OVX, and OVX-RES. The OXV-ZOL-RES had fewer osteoblasts and ALP- and OCN-cells than the SHAM and OVX-RES. The tartrate-resistant acid phosphatase (TRAP)-positive cells were reduced in the presence of ZOL (p < 0.05), while the TRAP mRNA levels increased with ZOL treatment, with or without resveratrol, compared with the other groups (p < 0.05). RES alone increased superoxide dismutase levels compared to OVX + ZOL and OVX + ZOL + RES (p < 0.05). In conclusion, resveratrol reduced the tissue impairment severity induced by ZOL; however, it could not prevent the occurrence of MRONJ.
本研究评估了白藜芦醇（RES）对唑来膦酸（ZOL）治疗的去卵巢（OVX）大鼠颌骨药物相关性骨坏死（MRONJ）的预防作用。50只大鼠分为五组：假手术组（n = 10）：未去卵巢+安慰剂；去卵巢组（n = 10）：去卵巢+安慰剂；去卵巢+RES组（n = 10）：去卵巢+白藜芦醇；去卵巢+ZOL组（n = 10）：去卵巢+安慰剂+唑来膦酸；去卵巢+RES+ZOL组（n = 10）：去卵巢+白藜芦醇+唑来膦酸。对左侧下颌骨进行显微CT、组织形态计量学和免疫组织化学分析。右侧通过qPCR分析骨标志物基因表达。与未接受ZOL的组相比，ZOL增加了坏死骨的百分比并减少了新形成的骨（p < 0.05）。RES影响了去卵巢+ZOL+RES组的组织愈合模式，减少了炎性细胞浸润，并改善了拔牙部位的骨形成。去卵巢-ZOL组的成骨细胞、碱性磷酸酶（ALP）和骨钙素（OCN）免疫反应性细胞低于假手术组、去卵巢组和去卵巢-RES组。去卵巢-ZOL-RES组的成骨细胞以及ALP和OCN细胞比假手术组和去卵巢-RES组少。在ZOL存在的情况下，抗酒石酸酸性磷酸酶（TRAP）阳性细胞减少（p < 0.05），而与其他组相比，无论有无白藜芦醇，ZOL治疗均使TRAP mRNA水平升高（p < 0.05）。与去卵巢+ZOL组和去卵巢+RES+ZOL组相比，单独使用RES可增加超氧化物歧化酶水平（p < 0.05）。总之，白藜芦醇降低了ZOL诱导的组织损伤严重程度；然而，它不能预防MRONJ的发生。
