Nutrition and Metabolic Disease Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Mol Neurobiol. 2024 Oct;61(10):7767-7784. doi: 10.1007/s12035-024-04048-0. Epub 2024 Mar 2.
Bisphenol A (BPA), an endocrine disruptor, is commonly used to produce epoxy resins and polycarbonate plastics. Continuous exposure to BPA may contribute to the development of diseases in humans and seriously affect their health. Previous research suggests a significant relationship between the increased incidence of neurological diseases and the level of BPA in the living environment. Syringic acid (SA), a natural derivative of gallic acid, has recently considered much attention due to neuromodulator activity and its anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Therefore, in this study, we aimed to investigate the effects of SA on oxidative stress, apoptosis, memory and locomotor disorders, and mitochondrial function, and to identify the mechanisms related to Alzheimer's disease (AD) in the brain of rats receiving high doses of BPA. For this purpose, male Wistar rats received BPA (50, 100, and 200 mg/kg) and SA (50 mg/kg) for 21 days. The results showed that BPA exposure significantly altered the rats' neurobehavioral responses. Additionally, BPA, by increasing the level of ROS, and MDA level, increased the level of oxidative stress while reducing the level of antioxidant enzymes, such as SOD, CAT, GPx, and mitochondrial GSH. The administration of BPA at 200 mg/kg significantly decreased the expression of ERRα, TFAM, irisin, PGC-1α, Bcl-2, and FNDC5, while it increased the expression of TrkB, cytochrome C, caspase 3, and Bax. Moreover, the Western blotting results showed that BPA increased the levels of P-AMPK, GSK3b, p-tau, and Aβ, while it decreased the levels of PKA, P-PKA, Akt, BDNF, CREB, P-CREB, and PI3K. Meanwhile, SA at 50 mg/kg reversed the behavioral, biochemical, and molecular changes induced by high doses of BPA. Overall, BPA could lead to the development of AD by affecting the mitochondria-dependent apoptosis pathway, as well as AMPK/PGC-1α/FNDC5 and CREB/BDNF/TrkB signaling pathways, and finally, by increasing the expression of tau and Aβ proteins. In conclusion, SA, as an antioxidant, significantly reduced the toxicity of BPA.
双酚 A（BPA）作为一种内分泌干扰物，常用于生产环氧树脂和聚碳酸酯塑料。持续暴露于 BPA 可能导致人类疾病的发展，并严重影响其健康。先前的研究表明，神经系统疾病发病率的增加与生活环境中 BPA 水平之间存在显著关系。丁香酸（SA）是没食子酸的天然衍生物，由于其具有神经调节剂活性以及抗氧化、抗凋亡和抗炎作用，最近受到了广泛关注。因此，在这项研究中，我们旨在研究 SA 对氧化应激、细胞凋亡、记忆和运动障碍以及线粒体功能的影响，并确定与大鼠大脑中 BPA 相关的阿尔茨海默病（AD）机制。为此，雄性 Wistar 大鼠接受 BPA（50、100 和 200mg/kg）和 SA（50mg/kg）21 天。结果表明，BPA 暴露显著改变了大鼠的神经行为反应。此外，BPA 通过增加 ROS 和 MDA 水平，增加氧化应激水平，同时降低 SOD、CAT、GPx 和线粒体 GSH 等抗氧化酶的水平。200mg/kg BPA 给药显著降低了 ERRα、TFAM、鸢尾素、PGC-1α、Bcl-2 和 FNDC5 的表达，而增加了 TrkB、细胞色素 C、caspase 3 和 Bax 的表达。此外，Western 印迹结果表明，BPA 增加了 P-AMPK、GSK3b、p-tau 和 Aβ 的水平，同时降低了 PKA、P-PKA、Akt、BDNF、CREB、P-CREB 和 PI3K 的水平。同时，50mg/kg 的 SA 逆转了高剂量 BPA 引起的行为、生化和分子变化。总之，BPA 可能通过影响线粒体依赖性细胞凋亡途径以及 AMPK/PGC-1α/FNDC5 和 CREB/BDNF/TrkB 信号通路，最终增加 tau 和 Aβ 蛋白的表达，导致 AD 的发生。综上所述，SA 作为一种抗氧化剂，显著降低了 BPA 的毒性。
