Monoaminergic systems activity and cellular defense mechanisms in the brainstem 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 subchronic oral exposure to MnCl2 200 mg/kg (3-month-old) and 30-100-200 mg/kg (20-month-old). In aged rats, manganese (Mn) significantly decreased 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 affected in young rats. In aged rats, individual total Mn doses/rat were inversely correlated with individual DA levels (r = -0.405) and GSH levels (r = -0.450). In conclusion, Mn induces changes in markers of monoaminergic 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 xanthine-oxidase on uric acid precursors.