Modulation of oxidative events by multivalent manganese complexes in braintissue

Manganese toxicity can evoke neuropsychiatric and neuromotor symptoms, whic h have frequently been attributed to profound oxidative stress in the dopam inergic system. However, the characterization of manganese as a pro-oxidant remains controversial because antioxidant properties also have been associ ated with this metal. The current study was designed to address these dispa rate findings concerning the oxidative properties of manganese. The apparen t ability of manganese in its divalent form to promote formation of reactiv e oxygen species (ROS) within a cortical mitochondrial-synaptosomal (P2) fr action was completely abolished by the addition of one five hundredth of it s molarity of desferroxamine (DFO), a trivalent metal chelator. This large ratio and the high specificity of DFO for trivalent metal ions discounted t he possibility of inhibition of ROS generation by direct sequestration of d ivalent manganese, and implied the trace presence of a trivalent metal. Fur ther analysis suggested that this trace metal was manganic rather than ferr ic ion. Ferric ion was able to dampen the reactive oxygen species-generatin g capacity of manganous chloride, whereas manganic ion markedly promoted th is property attributed to manganous ion. Such findings of the potent effect s of trace amounts of trivalent cations upon Mn2+-related free radical gene ration offer resolution of earlier disparate findings concerning the oxidat ive character of manganese. (C) 2001 Elsevier Science Inc.