Oxidative stress and cytotoxicity induced by catecholamines and L-DOPA
Oxidative stress is a condition of excessive formation of reactive oxygen species (ROS) and/or deficiency in antioxidant defense systems. Catecholamines and L-DOPA have been speculated to induce oxidative stress by generating excessively ROS via MAO-catalyzed oxidative deamination and via autoxidation. Many lines of evidence have linked oxidative stress and cytotoxicity induced by catecholamines and L-DOPA to various disorders, such as Parkinson's disease, atherosclerosis, etc. SOD activity, XO activity, and the level of lipid peroxidation in rat brains were not changed after treatment with R-($-$)-deprenyl or (±)-M-2-PP. It was demonstrated that R-($-$)-deprenyl, (±)-M-2-PP, and (±)-2-HxMP were unable to suppress the autoxidation of dopamine in vitro. These results indicated that R-($-$)-deprenyl, (±)-M-2-PP, and (±)-2-HxMP do not have in vivo and in vitro antioxidative effects. Neuroblastoma SH-SY5Y cells were used to assess the cytotoxicity of dopamine and L-DOPA and the effects of several antioxidants, R-($-$)-deprenyl, (±)-M-2-PP, and (±)-2-HxMP. Dopamine and L-DOPA were found to be cytotoxic to SH-SY5Y cells. Antioxidants, such as catalase and glutathione, were shown to protect SH-SY5Y cells against the cytotoxicity of dopamine and L-DOPA by scavenging ROS generated from the autoxidation of dopamine and L-DOPA. R-($-$)-Deprenyl, but not (±)-M-2-PP or (±)-2-HxMP, was found to potentiate the dopamine cytotoxicity towards SH-SY5Y cells. Endothelial CPA-47 cells were employed to investigate the cytotoxicity of adrenaline and noradrenaline. Autoxidation of adrenaline or noradrenaline was shown to induce endothelial injury. The cell death was probably not via an apoptotic process. Neuroblastoma SK-N-MC DAT cells, which express dopamine transporters, were used to examine the effect of intracellular dopamine. Dopamine, after being transported into the cells, was found to be cytotoxic to these cells. This result was further supported by the use of dopamine uptake blockers, nomifensine and methylphenidate. It was detected that there was a low level of MAO activity in these cells. The role of MAO in oxidative stress was not demonstrated, however, it has not been ruled out from the present study. The present studies support the hypothesis that oxidative stress and cytotoxicity induced by cateholamines and L-DOPA may involve in certain pathological conditions.