Protective effect of 3-butyl-6-bromo-1(3H)-isobenzofuranone on hydrogen peroxide-induced damage in PC12 cells.
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+)](i)), 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.
Gao
Yuan
Y
Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Zhang
Hong-Wei
HW
Qiao
Hai-Ling
HL
Wang
Wei
W
Chang
Jun-Biao
JB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D001572:Benzofurans; D018696:Neuroprotective Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C027125:3-n-butylphthalide; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D002118:Calcium