Oxidative stress, progressive damage in the substantia nigra and plasma dopamine oxidation, in rats chronically exposed to ozone

The purpose of our work was to determine the effects of oxidative stress on the neurodegeneration process in the substantia nigra, and to evaluate dopamine-oxidation metabolites in the plasma using a cyclic voltammetry (CV) technique. We have also studied the correlation between the increases in oxidized dopamine-species levels with the severity of lipid-peroxidation in the plasma. Sixty-four male Wistar rats were divided into four experimental groups and received air (Group I, control) or ozone (0.25 ppm) daily by inhalation for 4 h for 15 (Group II), 30 (Group III), and 60 (Group IV) days. The brains were processed for immunohistochemical location of dopamine and p53 in the substantia nigra. Plasma collected from these animals was assayed for oxidized dopamine products using CV and lipid-peroxidation levels were measured. Our results indicate that chronic exposure to low O3 doses causes that the number of dopaminergic neurons decreased, and p53-immunoreactive cells increases until 30 days; which was a function of the time of exposure to ozone. Oxidative stress produces a significant increase in the levels of the dopamine quinones (DAQs) that correlated well (r = 0.962) with lipid peroxides in the plasma during the study period. These results suggest that DAQ could be a reliable, peripheral oxidative indicator of nigral dopaminergic damage in the brain.