MANGANESE-INDUCED REACTIVE OXYGEN SPECIES - COMPARISON BETWEEN MN+2 AND MN+3

Manganese (Mn) is an essential element, the deficiency or excess of wh ich is known to cause neurotoxicity in experimental animals and man. T he mechanism of action of Mn neurotoxicity is still unclear. The prese nt study was designed to evaluate whether in vitro or in vivo exposure to Mn produced reactive oxygen species (ROS). We also sought to deter mine if a single injection of Mn produces changes in monoamines concen tration in different regions of rat brain. Adult Sprague-Dawley rats w ere dosed with 0, 50 or 100 mg/kg, ip with either MnCl2 (Mn+2) or MnOA c (Mn+3) and were sacrificed 1 h after the dose was administered. Brai ns were quickly removed and dissected for neurochemical analysis. ROS were measured by a molecular probe, 2',7'-dichlorofluorescein diacetat e (DCFH-DA), and monoamines and their metabolites were measured by HPL C/EC. In vitro exposure to MnCl2 (1-1000 mu M) produced dose-dependent increases of ROS in striatum whereas MnOAc produced similar increases at much lower concentrations (1-100 mu M) In vivo exposure to MnOAc ( Mn+3) produced significant increases of ROS in caudate nucleus and hip pocampus, whereas MnCl2 (Mn+2) produced significant effects only in hi ppocampus. Concentrations of dopamine, serotonin and their metabolites (DOPAC, HVA and 5-HIAA) were not altered with acute injections of eit her MnCl2 or MnOAc. These data suggest that both divalent and trivalen t manganese induce ROS, however, Mn+3 is an order of magnitude more po tent than Mn+2. (C) 1995 Academic Press Limited