title: Effects of allopurinol on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurochemical changes in the striatum and in the brainstem of the rat.
abstract: 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.
authors.affiliation: Institute of Pharmacology, University of Sassari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Miele
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.forename: R
authors.initials: R
authors.lastname: Migheli
authors.forename: S
authors.initials: S
authors.lastname: Sircana
authors.forename: D
authors.initials: D
authors.lastname: Zangani
authors.forename: G L
authors.initials: GL
authors.lastname: Fresu
authors.forename: M S
authors.initials: MS
authors.lastname: Desole
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
chemical_list: D007042:Hypoxanthines; D014970:Xanthines; D014527:Uric Acid; D019271:Hypoxanthine; D000493:Allopurinol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005978:Glutathione; D001205:Ascorbic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D009638:Norepinephrine