Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Targeted Drug Delivery Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Phytother Res. 2021 Feb;35(2):996-1009. doi: 10.1002/ptr.6861. Epub 2020 Sep 7.
This study was designed to assess bisphenol A (BPA)-induced vascular toxicity, the effectiveness of green tea extract and epigallocatechin gallate (EGCG) against BPA toxicity, and possible underlying mechanisms. In isolated rat aorta, contractile and relaxant responses as well as malondialdehyde levels were evaluated. Cell viability and effects on the protein levels of apoptotic (bax, bcl2, and caspase-3), autophagic (LC3), and cell adhesion molecules were calculated using the MTT method and western blotting in human umbilical vein endothelial cells (HUVECs). BPA increased aorta MDA levels (p < .0001) and decreased vascular responses to KCl [20 and 40 mM (p < .0001), 80 mM (p < .001)], phenylephrine [10 , 10 , and 10 M (p < .001), 10 and 10 M (p < .0001)], and acetylcholine [10 M (p < .01), 10 and 10 M (p < .0001)]. In HUVECs, BPA enhanced the levels of LC3A/B, bax/bcl2 ratio, cleaved caspase-3, and vascular cell adhesion molecule-1. Green tea extract, EGCG, and vitamin E co-treatment with BPA diminished the toxic effects of BPA. These findings provide evidence that green tea extract and EGCG possess beneficial effects in preventing BPA-induced vascular toxicity through increasing the antioxidant activities and the regulation of signaling pathways.
本研究旨在评估双酚 A(BPA)诱导的血管毒性、绿茶提取物和表没食子儿茶素没食子酸酯(EGCG)对 BPA 毒性的有效性,以及可能的潜在机制。在分离的大鼠主动脉中,评估了收缩和舒张反应以及丙二醛水平。使用 MTT 法和 Western blot 法在人脐静脉内皮细胞(HUVECs)中计算细胞活力以及对凋亡(bax、bcl2 和 caspase-3)、自噬(LC3)和细胞黏附分子蛋白水平的影响。BPA 增加主动脉 MDA 水平(p < .0001),并降低血管对 KCl [20 和 40 mM(p < .0001),80 mM(p < .001)]、苯肾上腺素 [10、10 和 10 M(p < .001),10 和 10 M(p < .0001)]和乙酰胆碱 [10 M(p < .01),10 和 10 M(p < .0001)]的反应。在 HUVECs 中,BPA 增强了 LC3A/B、bax/bcl2 比值、裂解 caspase-3 和血管细胞黏附分子-1 的水平。绿茶提取物、EGCG 和维生素 E 与 BPA 共同处理可减轻 BPA 的毒性作用。这些发现提供了证据,表明绿茶提取物和 EGCG 通过增加抗氧化活性和调节信号通路,具有预防 BPA 诱导的血管毒性的有益作用。