Exposure of striatal [corrected] synaptosomes to L-dopa increases levels of oxidized glutathione

Incubation of striatal synaptosomes with L-dopa and glucose in either the presence or absence of 10 microM reserpine resulted in a rise in the level of oxidized glutathione (GSSG) within the isolated tissue pellet. The rise in GSSG was concentration dependent in the range of 0.04-1.0 mM L-dopa. With 1.0 mM L-dopa in the presence of reserpine, the GSSG level was elevated by 7.0 +/- 0.7 pmol/mg original striatal tissue, which corresponds to an increase of 38.0 +/- 4.5% compared with control. The rise in GSSG reflects an oxidative stress. The oxidation of dopamine by monoamine oxidase generates H2O2, which is normally detoxified by glutathione peroxidase to yield GSSG. In the presence of clorgyline or pargyline (two monoamine oxidase inhibitors), the rise in GSSG was suppressed by 88-92%, as was the formation of DOPAC. NSD-1055 and carbidopa (two inhibitors of dopa-decarboxylase) also significantly suppressed (50-60%) the rise in GSSG. These data show that the synthesis of dopamine from L-dopa, with subsequent catabolism of dopamine, can evoke a significant rise in the level of GSSG, which reflects the oxidant stress associated with monoamine oxidase activity.