Protective effect of 3-butyl-6-bromo-1(3H)-isobenzofuranone on hydrogen peroxide-induced damage in PC12 cells

Abstract: 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(H2O2)- induced oxidative damage was investigated in PC12 cells. Following exposure of the cells to H2O2, 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 Ca2+ concentration ([Ca2+]i), as well as cell apoptosis were observed. However, pretreatment of cells with Br-NBP prior to H2O2 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 H2O2-induced cytotoxicity in PC12 cells, suggesting that the compound may be a potential therapeutic agent for diseases induced by oxidative damage. [Copyright &y& Elsevier]