Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Brain Res. 2010 Oct 28;1358:239-47. doi: 10.1016/j.brainres.2010.08.043. Epub 2010 Aug 21.
Oxidative stress, an imbalance toward the prooxidant side of the prooxidant/antioxidant homeostasis, occurs in several brain neurodegenerative disorders. The protective effect of 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP), a derivative compound of l-3-n-butylphthalide (NBP), on the hydrogen peroxide(H(2)O(2))- induced oxidative damage was investigated in PC12 cells. Following exposure of the cells to H(2)O(2), there was a significant reduction in cell survival,activities of glutathione peroxidase (GSH-px) and mitochondria membrane potential(MMP), in contrast, the increased levels in the leakage of lactate dehydrogenase (LDH), malondialdehyde (MDA) contents, nitric oxide (NO) productions, intracellular reactive oxygen species (ROS), intracellular Ca(2+) concentration (Ca(2+)), as well as cell apoptosis were observed. However, pretreatment of cells with Br-NBP prior to H(2)O(2) exposure attenuated all the changes mentioned above in a concentration-dependent manner except no effect on activities of GSH-px. Br-NBP exhibited the protective effect against H(2)O(2)-induced cytotoxicity in PC12 cells, suggesting that the compound may be a potential therapeutic agent for diseases induced by oxidative damage.
氧化应激是指在氧化还原平衡的促氧化剂侧发生的一种失衡状态,存在于几种脑部神经退行性疾病中。3-正丁基-6-溴-1(3H)-异苯并呋喃酮(Br-NBP)是 l-3-正丁基邻苯二甲酸内酯(NBP)的衍生物化合物,本研究旨在探讨其对过氧化氢(H₂O₂)诱导的氧化损伤的保护作用。将细胞暴露于 H₂O₂后,细胞存活率、谷胱甘肽过氧化物酶(GSH-px)活性和线粒体膜电位(MMP)显著降低,而乳酸脱氢酶(LDH)漏出、丙二醛(MDA)含量、一氧化氮(NO)生成、细胞内活性氧(ROS)、细胞内钙离子浓度([Ca²⁺]i)和细胞凋亡水平则升高。然而,与 H₂O₂ 孵育前用 Br-NBP 预处理细胞可呈浓度依赖性减轻上述所有变化,除了对 GSH-px 活性无影响。Br-NBP 对 H₂O₂ 诱导的 PC12 细胞毒性具有保护作用,表明该化合物可能是一种治疗氧化损伤诱导疾病的潜在治疗剂。