MONOAMINERGIC SYSTEMS ACTIVITY AND CELLULAR DEFENSE-MECHANISMS IN THEBRAIN-STEM OF YOUNG AND AGED RATS SUBCHRONICALLY EXPOSED TO MANGANESE

In 3- and 20-month-old male Wistar rats, levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), ascorbic acid (AA), dehydroascorbic acid (DHAA), uric acid and glutathione (GSH) were determined by HPLC in the brainstem after s ubchronic oral exposure to MnCl2 200 mg/kg (3-month-old) and 30-100-20 0 mg/kg (20-month-old). In aged rats, manganese (Mn) significantly dec reased levels of NA, DA and GSH and increased 5-HIAA/5-HT ratio values and DHAA and uric acid levels. All these parameters were scarcely aff ected in young rats. In aged rats, individual total Mn doses/rat were inversely correlated with individual DA levels (r = -0.405) and GSH le vels (r = -0.450). In conclusion, Mn induces changes in markers of mon oaminergic systems activity in the brainstem of aged rats considerably greater than in young rats. The increase in AA oxidation and decrease in GSH levels are consistent with a Mn-induced increase in formation of reactive oxygen species. The increase in uric acid levels provides evidence that one of these species might arise from the activity of xa nthine-oxidase on uric acid precursors.