DOPAMINERGIC SYSTEM ACTIVITY AND CELLULAR DEFENSE-MECHANISMS IN THE STRIATUM AND STRIATAL SYNAPTOSOMES OF THE RAT SUBCHRONICALLY EXPOSED TOMANGANESE

In 6-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphe nylacetic acid (DOPAC), ascorbic acid (AA). dehydroascorbic acid (DHAA ), uric acid and glutathione (GH) were determined by HPLC in the stria tum and striatal synaptosomes after subchronic oral exposure to MnCl2 50-100-150 mg/kg. Mn significantly decreased levels of DA and GSH and increased levels of DHAA and uric acid both in the striatum and synapt osomes. In synaptosomes, individual total Mn doses/rat were directly c orrelated with individual DOPAC/DA ratio values (r = +0.647), uric aci d (r = +0.532) and DHAA levels (r = +0.889) and inversely correlated w ith DA (r = -0.757) and GSH levels (r = -0.608). In turn, GSH levels w ere inversely correlated with uric acid (r = -0.451) and DHAA levels ( r = -0.460). In conclusion, the response of striatal cellular defense mechanisms (increase in AA oxidation, decrease in GSH levels) correlat ed well with changes in markers of dopaminergic system activity and in crease in uric acid levels. The latter provides evidence of an Mn-indu ced oxidative stress mediated by xanthine oxidase.