L-DOPA CYTOTOXICITY TO PC12 CELLS IN CULTURE IS VIA ITS AUTOXIDATION

The mechanism of cytotoxicity of L-DOPA was studied in the rat pheochr omocytoma PC12 cell line. The cytotoxicity of L-DOPA to PC12 cells was time and concentration dependent. Carbidopa, which inhibited the conv ersion of L-DOPA to dopamine, did not protect against L-DOPA cytotoxic ity in PC12 cells. Furthermore, clorgyline, a selective inhibitor of m onoamine 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 for med from L-DOPA. Catalase or superoxide dismutase each partially prote cted against L-DOPA toxicity in PC12 cells. In combination, the effect s were synergistic and provided almost total protection against cytoto xicity. 6-Cyano-7-nitroquinoxaline-2,3-dione, an antagonist of non-NMD A receptors, did not protect against L-DOPA toxicity. These data sugge st that toxicity of L-DOPA is most likely due to the action of free ra dicals formed as a result of its autoxidation. Furthermore, these find ings suggest that patients on long-term L-DOPA therapy are potentially at risk from the toxic intermediates formed as a result of its autoxi dation.