Protective effects of antioxidants on striatal dopamine release induced by organophosphorus pesticides

Abstract

Although the toxic effects of organophosphorus (OP) pesticides have been classically attributed to inhibition of the acetylcholinesterase, other neurotoxic mechanisms, as oxidative stress can also occur. Here we evaluated if antioxidants prevent the excessive dopamine release induced by OP pesticides in conscious and freely moving rats, using cerebral microdialysis technique. Intrastriatal infusion of paraoxon (5 mM), glufosinate (10 mM) or glyphosate (5 mM) significantly increased the dopamine release (1006 ± 106%, 991 ± 142%, and 1164 ± 128%, relative to baseline, respectively). To evaluate if these increased dopamine release could be related to oxidative stress, we pretreated animals with antioxidants glutathione (GSH, 400 or 800 μM), dithiothreitol (DTT, 5 or 10 μM), trolox (1 or 3 mM), and α-lipoic acid (ALA, 400 or 800 μM) before administration of OP pesticides. Intrastriatal administration of the antioxidants GSH, DTT, trolox, and ALA was highly effective in preventing the glyphosate and glufosinate-induced dopamine overflow. However, only GSH (800 μM) significantly decreased the effect of paraoxon on dopamine levels. The high toxicity of this pesticide and the low concentrations used could explain this lack of effect in our experimental conditions. The fact that ROS scavengers prevent the excessive dopamine release induced by OP pesticides, further supports the view that dopamine overflow can cause neuronal damage mediated, at least in part, by oxidative stress.