l‐DOPA Cytotoxicity to PC12 Cells in Culture Is via Its Autoxidation

Abstract

The mechanism of cytotoxicity of l‐DOPA was studied in the rat pheochromocytoma PC12 cell line. The cytotoxicity of l‐DOPA to PC12 cells was time and concentration dependent. Carbidopa, which inhibited the conversion of l‐DOPA to dopamine, did not protect against l‐DOPA cytotoxicity in PC12 cells. Furthermore, clorgyline, a selective inhibitor of monoamine oxidase type A, and pargyline, an inhibitor of both monoamine oxidase types A and B, both did not have an effect on l‐DOPA toxicity. These findings suggest that cytotoxicity was not due to dopamine formed from l‐DOPA. Catalase or superoxide dismutase each partially protected against l‐DOPA toxicity in PC12 cells. In combination, the effects were synergistic and provided almost total protection against cytotoxicity. 6‐Cyano‐7‐nitroquinoxaline‐2,3‐dione, an antagonist of non‐NMDA receptors, did not protect against l‐DOPA toxicity. These data suggest that toxicity of l‐DOPA is most likely due to the action of free radicals formed as a result of its autoxidation. Furthermore, these findings suggest that patients on long‐term l‐DOPA therapy are potentially at risk from the toxic intermediates formed as a result of its autoxidation.

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

“…The catecholamines have been shown to be toxic because of their ability to oxidize and produce reactive oxygen species and quinones in contrast to the other tested structural analogues of l-dopa that do not undergo autooxidation (Basma et al, 1995;Han et al, 1996;Mena et al, 1997). We hypothesized that l-dopa and the other catecholamines activated the yeast mating MAPK via autooxidation by forming reactive oxygen species.…”

The role of L-DOPA in plants

“…Some studies report that the beneficial effect of L-DOPA on Parkinson disease is counterbalanced by the strong oxidative damage generated over a long period of drug administration. [13][14][15][16] L-DOPA has also been found at high levels in fava bean (Vicia faba L.), one of the oldest crops in Europe, traditionally used as weld beans for animal feed and human food, and as broad beans for direct human consumption. The content and distribution of this non-protein amino acid were examined in cotyledons and embryo axis along the germination and seedling growth of Vicia faba varieties Alameda and Brocal.…”

Antioxidant potential of melatonin enhances the response to L-dopa in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-parkinsonian mice

“…L-dopa is used in PD therapy, since it can be converted enzymatically to dopamine, restoring its levels. Autoxidation, increasing, even more, the oxidative stress situation at nigrostriatal sites and L-dopa-treated patients will be at greater risk [6]. With regard to antioxidant treatment, L-dopa administration in rats induces formation of L-dopa-semiquinone, which can act as oxidant, decreasing dopamine and ascorbic acid levels [46].…”

“…In the grid walking test, statistical analysis using ANOVA indicated a difference in the percentage of foot slip errors after treatment with the selected regimens at the two time points, at week 4 [F (6,28 Fig. 3C).…”