Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Phytother Res. 2018 Dec;32(12):2396-2407. doi: 10.1002/ptr.6175. Epub 2018 Aug 16.
The underlying mechanism of Bisphenol A (BPA)-induced vascular toxicity and the protective role of grape seed extract (GSE) and resveratrol were investigated in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of GSE and resveratrol. Then, BPA was added to the cells and cell viability and effects on the protein level of cell adhesion molecules were measured through MTT and western blotting. Animals were randomly divided into control, GSE (3 and 12 mg·kg ·day ip), resveratrol (100 mg·kg ·day ip), BPA (35 mg·kg ·day , gavage), BPA plus GSE (3, 6, and 12 mg·kg ·day ip), BPA plus resveratrol (25, 50, and 100 mg·kg ·day ip), and BPA plus vitamin E (200 IU/kg per every other day ip). After 2 months, contractile and relaxant responses were evaluated on the isolated aorta. BPA increased the level of aorta malondialdehyde (p < 0.001) and decreased vascular responses to KCl (p < 0.01), phenylephrine (p < 0.001), and acetylcholine (p < 0.01). In HUVECs, BPA (IC : 220 μM) increased protein level of vascular cell adhesion molecule (p < 0.05) and cleaved capase3 (p < 0.001). GSE, resveratrol, and vitamin E cotreatment restored toxic effects of BPA in some levels. BPA vascular toxicity was attributed to lipid peroxidation and endothelial dysfunction. The protective role of GSE and resveratrol against BPA-endothelial dysfunction could be attributed to their potent antioxidant properties.
双酚 A (BPA) 诱导的血管毒性的潜在机制以及葡萄籽提取物 (GSE) 和白藜芦醇的保护作用在体外和体内进行了研究。将人脐静脉内皮细胞 (HUVEC) 暴露于不同浓度的 GSE 和白藜芦醇中。然后，向细胞中加入 BPA，通过 MTT 和 Western blot 测量细胞活力和细胞黏附分子蛋白水平的变化。动物随机分为对照组、GSE (3 和 12 mg·kg·day ip)、白藜芦醇 (100 mg·kg·day ip)、BPA (35 mg·kg·day ，灌胃)、BPA 加 GSE (3、6 和 12 mg·kg·day ip)、BPA 加白藜芦醇 (25、50 和 100 mg·kg·day ip)和 BPA 加维生素 E (200 IU/kg 每隔一天 ip)。2 个月后，评估离体主动脉的收缩和舒张反应。BPA 增加了主动脉丙二醛的水平 (p<0.001)，并降低了血管对 KCl (p<0.01)、苯肾上腺素 (p<0.001)和乙酰胆碱 (p<0.01)的反应。在 HUVEC 中，BPA (IC: 220 μM) 增加了血管细胞黏附分子的蛋白水平 (p<0.05)和裂解的 capase3 (p<0.001)。GSE、白藜芦醇和维生素 E 共同处理在某些水平上恢复了 BPA 的毒性作用。BPA 血管毒性归因于脂质过氧化和内皮功能障碍。GSE 和白藜芦醇对 BPA 内皮功能障碍的保护作用可能归因于它们强大的抗氧化特性。
