Effect of oxidative stress induced by L-dopa on endogenous antioxidants in PC-12 cells.

The mechanism of action of many drugs of abuse involves the dopaminergic pathway. One method of increasing dopamine in brain is by ingestion of L-dopa (3,4-dihydroxy-L-phenylalanine). Interestingly, both dopamine and L-dopa cause oxidative stress which is also a factor in drug-induced damage. Oxidative stress can be reduced by the antioxidant activities of vitamins C (ascorbate) and E (tocopherols). However, the interactions between L-dopa and tocopherols and ascorbate are not well understood. In this article, PC-12 cells (as models of neurons) were cultured for 21 hours with ascorbate (400 microM) and/or alpha tocopherol (25 microM) and in the presence or absence of L-dopa (250 microM). After incubation, cells were harvested and analyzed for the various biochemical components by HPLC. As expected, the addition of L-dopa resulted in an almost threefold increase in cellular dopamine content. Addition of alpha tocopherol resulted in marked increase in cellular tocopherol. Similarly, addition of ascorbate substantially increased its cellular concentration. These increases were strongly attenuated by the presence of L-dopa in the medium. The data indicate that: (a) the uptake systems for ascorbate and tocopherols in these cells are inhibited by L-dopa and/or (b) L-dopa treatment causes an increase in the rate of utilization of the two nutrients. Thus L-dopa modulates the cellular dynamics of ascorbate and tocopherol altering cellular antioxidant protection.