ALLOPURINOL PROTECTS AGAINST MANGANESE-INDUCED OXIDATIVE STRESS IN THE STRIATUM AND IN THE BRAIN-STEM OF THE RAT

Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic acid, glutathione (GSH), noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine were determined in the striatum and/or in the brainstem of 3-month-old male Wistar rats given manganese (MnCl2, 200 mg/kg/day for 7 days by gavage) alone or associated with allopurinol. Allopurinol alone (300 mg/kg/day for 4 days by gavage) decreased uric acid and increased xanthine levels both in the striatum and in the brainstem; moreover, allopurinol decreased the striatal DOPAC + HVA/DA ratio. Allopurinol antagonised the Mn-induced: (a) increase in the DOPAC + HVA/DA ratio; (b) increase in uric acid levels and AA oxidation; and (c) decrease in GSH and NA levels. We conclude that allopurinol may protect against Mn-induced oxidative stress by inhibiting both DA oxidative metabolism and xanthine oxidase-mediated formation of reactive oxygen species.