D'Amico Emira, Cinquini Chiara, Petrini Morena, Barone Antonio, Iezzi Giovanna, D'Ercole Simonetta, De Filippis Barbara, Pierfelice Tania Vanessa
Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Department of Surgical, Medical, Molecular Pathologies and of the Critical Needs, School of Dentistry, University of Pisa, 56126 Pisa, Italy.
Metabolites. 2024 Jun 22;14(7):350. doi: 10.3390/metabo14070350.
Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound healing. Resveratrol (RSV) is known for its antioxidant properties, but its limited bioavailability hinders its clinical use. This study investigated the potential of two RSV derivatives ( and ) to address these limitations. The antioxidant abilities of and (5 μM) against DEX-induced oxidative stress (200 μM) were evaluated in human gingival fibroblasts (hGFs) and osteoblasts (hOBs). The effects of these compounds on cell viability, morphology, ROS levels, SOD activity, gene expression, and collagen production were evaluated. RSV derivatives, under DEX-induced oxidative stress condition, improved cell growth at 72 h (191.70 ± 10.92% for +DEX and 184.80 ± 13.87% for +DEX), morphology, and SOD activity (77.33 ± 3.35 OD for +DEX; 76.87 ± 3.59 OD for +DEX at 1 h), while reducing ROS levels (2417.33 ± 345.49 RFU for +DEX and 1843.00 ± 98.53 RFU at 4 h), especially in hOBs. The co-treatment of RSV or derivatives with DEX restored the expression of genes that were downregulated by DEX, such as HO-1 (1.76 ± 0.05 for +DEX and 1.79 ± 0.01 for +DEX), CAT (0.97 ± 0.06 for +DEX and 0.99 ± 0.03 for +DEX), NRF2 (1.62 ± 0.04 for +DEX and 1.91 ± 0.05 for +DEX), SOD1 (1.63 ± 0.15 for +DEX and 1.69 ± 0.04 for +DEX). In addition, and preserved collagen production (111.79 ± 1.56 for +DEX and 122.27 ± 1.56 for +DEX). In conclusion, this study suggests that the RSV derivatives and hold promise as potential antioxidant agents to counteract DEX-induced oxidative stress. These findings contribute to the development of novel therapeutic strategies for managing oxidative stress-related oral conditions.
氧化应激和高水平的活性氧(ROS)与各种与年龄相关的疾病和慢性疾病有关,包括对口腔组织的损害。地塞米松(DEX)是牙科中广泛使用的糖皮质激素,可能会产生副作用,如ROS生成增加和伤口愈合延迟。白藜芦醇(RSV)以其抗氧化特性而闻名,但其有限的生物利用度阻碍了其临床应用。本研究调查了两种RSV衍生物( 和 )解决这些局限性的潜力。在人牙龈成纤维细胞(hGFs)和成骨细胞(hOBs)中评估了 和 (5 μM)对DEX诱导的氧化应激(200 μM)的抗氧化能力。评估了这些化合物对细胞活力、形态、ROS水平、超氧化物歧化酶(SOD)活性、基因表达和胶原蛋白产生的影响。在DEX诱导的氧化应激条件下,RSV衍生物在72小时时改善了细胞生长(+DEX组为191.70±10.92%,+DEX组为184.80±13.87%)、形态和SOD活性(+DEX组在1小时时为77.33±3.35 OD;+DEX组为76.87±3.59 OD),同时降低了ROS水平(+DEX组在4小时时为2417.33±345.49 RFU,为1843.00±98.53 RFU),尤其是在hOBs中。RSV或其衍生物与DEX联合处理恢复了被DEX下调的基因的表达,如血红素加氧酶-1(HO-1)(+DEX组为1.76±0.05,+DEX组为1.79±0.01)、过氧化氢酶(CAT)(+DEX组为0.97±0.06,+DEX组为0.99±0.03)、核因子E2相关因子2(NRF₂)(+DEX组为1.62±0.04,+DEX组为1.91±0.05)、超氧化物歧化酶1(SOD1)(+DEX组为1.63±0.15,+DEX组为1.69±0.04)。此外, 和 保留了胶原蛋白的产生(+DEX组为111.79±1.56,+DEX组为122.27±1.56)。总之,本研究表明RSV衍生物 和 有望作为潜在的抗氧化剂来对抗DEX诱导的氧化应激。这些发现有助于开发用于管理与氧化应激相关的口腔疾病的新型治疗策略。