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.