Effects of selegiline on antioxidant enzymes in the nigrostriatum in rat

Abstract

Selegiline, a therapeutic agent of Parkinson's disease, is known to have neuroprotective properties that may involve its regulatory effects on antioxidant enzymes. Here, the activities of catalase (CAT), Cu,Zn- and Mn-superoxide dismutase (SOD1 and SOD2) in the striatum, cortex and hippocampus of 8- and 25-week-old rats, and SOD activities in midbrain slice cultures were evaluated. After Fisher 344 rats were given daily subcutaneous injections of selegiline (2 mg/kg) or L-dopa (10 mg/kg) plus benserazide (2.5 mg/kg) over a period of 21 days, CAT and SOD activities were measured. Organotypic slice cultures were prepared with a tissue chopper from brain in postnatal day 3 Wistar rats, and maintained for 16–17 days in a 5% CO 2 humidified atmosphere at 34 °C. Slice cultures were incubated with selegiline (10 −11–10 −5 M) for 24 h. Selegiline significantly increased CAT and SOD2 activities in the striatum, but not in the cortex and hippocampus, of 25-week-old rats. In contrast, selegiline failed to increase CAT and SOD activities in three brain regions of 8-week-old rats, whereas treatment with L-dopa resulted in a significant increase in the activities of SOD1 in the striatum of 8-week-old rats. In midbrain slice cultures, selegiline increased SOD1 and SOD2 activities with maximal effective concentrations of 10 −8 and 10 −10 M, respectively. These in vitro effects of selegiline exhibited a bell-shaped concentration dependence. These results suggest that selegiline can decrease oxidative stress in the striatum and the midbrain by augmenting various antioxidant systems, each of which responds optimally to different concentrations of selegiline.