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

作者：Alie N. Basma, Erick J. Morris, William J. Nicklas, Herbert M. Geller · 发表于：Journal of Neurochemistry · 年份：1995 · DOI：10.1046/j.1471-4159.1995.64020825.x · 被引用次数：226 · 研究领域：Neurotransmitter Receptor Influence on Behavior、Neuroscience and Neuropharmacology Research、Receptor Mechanisms and Signaling

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.