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.
Environ Sci Pollut Res Int. 2023 Sep;30(42):95789-95800. doi: 10.1007/s11356-023-29162-9. Epub 2023 Aug 9.
Acrylamide (ACR) is known to be a neurotoxic agent for humans and animals that has many applications in industry. Alpha-mangostin is a natural antioxidant that is extracted from mangosteen. This study aimed to investigate the protective effects of alpha-mangostin against ACR-induced neurotoxicity in rats and PC12 cells. Male Wistar rats were used in this investigation for 11 days, divided into 8 groups: 1. control group (normal saline), 2. ACR (50 mg/kg, i.p.), 3-6. ACR + alpha-mangostin (20, 40, 60 mg/kg, p.o.), 7. ACR + vitamin E (200 mg/kg, i.p., every other day) 8. alpha-mangostin (60 mg/kg, p.o.). On the last day of the study, the behavioral test was performed. The amounts of malondialdehyde (MDA) and glutathione (GSH) were measured. Also, the effects of ACR and alpha-mangostin were assessed by MTT assay on PC12 cells, and the levels of reactive oxygen species (ROS), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 proteins were measured by Western blotting. Receiving ACR caused motor disorders in animals, increased MDA, and decreased GSH levels of the cerebral cortex versus the control group. Alpha-mangostin (60 mg/kg) reduced ACR motility disorders, MDA amounts, and augmented GSH levels. The concurrent administration of vitamin E and ACR reduced gait score, MDA level, and amplified GSH content versus the ACR group. In the in vitro section, alpha-mangostin (1.25 µM, 24 h) increased cell viability, attenuated ROS, Bax/Bcl-2, and cleaved caspase-3 levels versus the ACR group. Alpha-mangostin reduced the toxicity of ACR by inhibiting oxidative stress and apoptosis. Therefore, it could be a promising compound for managing ACR-induced neurotoxicity.
丙烯酰胺(ACR)已知对人类和动物具有神经毒性,并且在工业中有许多应用。α-倒捻子素是一种从山竹果中提取的天然抗氧化剂。本研究旨在探讨α-倒捻子素对大鼠和 PC12 细胞中 ACR 诱导的神经毒性的保护作用。本研究使用雄性 Wistar 大鼠进行了 11 天的研究,分为 8 组:1. 对照组(生理盐水),2. ACR(50mg/kg,腹腔注射),3-6. ACR+α-倒捻子素(20、40、60mg/kg,口服),7. ACR+维生素 E(200mg/kg,每两天腹腔注射一次),8. α-倒捻子素(60mg/kg,口服)。在研究的最后一天,进行了行为测试。测量了丙二醛(MDA)和谷胱甘肽(GSH)的含量。还通过 MTT 测定评估了 ACR 和 α-倒捻子素对 PC12 细胞的影响,并通过 Western 印迹法测定了活性氧(ROS)、B 细胞淋巴瘤 2(Bcl-2)、Bcl-2 相关 X 蛋白(Bax)和裂解的 caspase-3 蛋白的水平。接受 ACR 会导致动物运动障碍,增加大脑皮质 MDA 并降低 GSH 水平与对照组相比。α-倒捻子素(60mg/kg)可减少 ACR 运动障碍、MDA 量并增加 GSH 水平。与 ACR 组相比,同时给予维生素 E 和 ACR 可降低步态评分、MDA 水平并放大 GSH 含量。在体外部分,α-倒捻子素(1.25μM,24 小时)增加细胞活力,减弱 ROS、Bax/Bcl-2 和裂解的 caspase-3 水平与 ACR 组相比。α-倒捻子素通过抑制氧化应激和细胞凋亡减轻 ACR 的毒性。因此,它可能是一种有前途的化合物,可用于治疗 ACR 诱导的神经毒性。