Neuroprotection by Polynitrogen Manganese Complexes: Regulation of Reactive Oxygen Species-Related Pathways

Cell death in the central nervous system causes neurologic diseases, in which reactive oxygen species (ROS) play a critical role by either inducing cellular oxidative stress or by increasing the cell tolerance against insult. Neurologic diseases may potentially be treated by regulating ROS levels in a certain range with small molecules. We studied preconditioning with two polynitrogen manganese complexes ( 1 and 2 ) to regulate intracellular ROS levels in the protection of both the differentiated rat pheochromocytoma cell line (PC12 cells) and neurons against H 2 O 2 -induced apoptosis. Pre-treatment with the two complexes attenuated the cell apoptosis caused by H 2 O 2 . And the ROS-related neuroprotective mechanisms were explored. Both complexes activate the hypoxia inducible factor-related pathways and increase the cell adaptation to oxidative stress. Pre-treatment with complex 1 eliminated intracellular ROS, which also activated antioxidase system, while short-term incubation of complex 2 , generated low levels of ROS leading to cell survival.