Oxidative damage caused by free radicals produced during catecholamine autoxidation: Protective effects of O-methylation and melatonin

Catecholamine autoxidation produces reactive oxygen species that have been implicated in the loss of dopaminergic neurons in the nigrostriatal region of the brain that occurs during normal aging and in Parkinsonʹs disease. In the present study, the potential protective effects of catecholamine O-methylation and of melatonin against catecholamine autoxidation-induced protein damage were assessed in vitro using the oxygen radical absorbance capacity (ORAC) assay. The rate of oxidation of the fluorescent protein porphyridium cruentum β-phycoerythrin (β-PE) caused by the oxidizing agent CUS04 was shown to be accelerated by addition of the catecholamines dopamine and image-dopa. Replacement of dopamine and image-dopa in the assay with their O-methylated metabolites 3-O-methyldopamine and 3-O-methyldopa significantly decreased the rate of β-PE oxidation. When melatonin was added to the ORAC assay in combination with dopamine or image-dopa, the rate of β-PE oxidation was decreased as well. These findings were consistent with the following interpretations: (1) O-methylated catecholamines are less susceptible to autoxidation than their nonmethylated precursors, and (2) melatonin, which has recently been shown to be a powerful antioxidant, is capable of scavenging free radicals produced during catecholamine autoxidation. These findings suggest that O-methylation and melatonin may be important components of the brainʹs antioxidant defenses against catecholamine autoxidation and may protect against consequent dopaminergic neurodegeneration.