Manganese-induced reactive oxygen species: comparison between Mn+2 and Mn+3

Abstract

Manganese (Mn) is an essential element, the deficiency or excess of which is known to cause neurotoxicity in experimental animals and man. The mechanism of action of Mn neurotoxicity is still unclear. The present study was designed to evaluate whether in vitro or in vivo exposure to Mn produced reactive oxygen species (ROS). We also sought to determine if a single injection of Mn produces changes in monoamines concentration in different regions of rat brain. Adult Sprague-Dawley rats were dosed with 0, 50 or 100 mg/kg, ip with either MnCl2 (Mn+2) or MnOAc (Mn+3) and were sacrificed 1 h after the dose was administered. Brains were quickly removed and dissected for neurochemical analysis. ROS were measured by a molecular probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), and monoamines and their metabolites were measured by HPLC/EC. In vitro exposure to MnCl2 (1-1000 microM) produced dose-dependent increases of ROS in striatum whereas MnOAc produced similar increases at much lower concentrations (1-100 microM). In vivo exposure to MnOAc (Mn+3) produced significant increases of ROS in caudate nucleus and hippocampus, whereas MnCl2 (Mn+2) produced significant effects only in hippocampus. Concentrations of dopamine, serotonin and their metabolites (DOPAC, HVA and 5-HIAA) were not altered with acute injections of either MnCl2 or MnOAc. These data suggest that both divalent and trivalent manganese induce ROS, however, Mn+3 is an order of magnitude more potent than Mn+2.