EFFECTS OF ALLOPURINOL ON 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)-INDUCED NEUROCHEMICAL CHANGES IN THE STRIATUM AND IN THE BRAIN-STEM OF THE RAT

Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic acid (DHAA), glutathione (GSH), noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP(+)) were determined in the striatum and/or in the brainstem of 3-month-old male Wistar rats, given allopurinol (500 mg/kg day by gavage) for 3 days before a single MPTP 52 mg/kg dose i.p. Allopurinol alone decreased uric acid and hypoxanthine levels in the striatum and in the brainstem; moreover, allopurinol increased AA oxidation and decreased striatal DA metabolites. Allopurinol affected neither regional MPTP and MPP(+) levels nor the MPTP-induced inhibition of striatal DA oxidative metabolism. On the contrary, the MPTP-induced increase in uric acid levels and decrease in xanthine, hypoxanthine and NA levels were fully antagonised. Such findings demonstrate that the claimed MPP(+)-induced oxidative stress mediated by xanthine oxidase may be involved at least in the NA depletion; moreover, uric acid may have a physiological role as an active component of the neuronal antioxidant pool.