title: Further investigation of allopurinol effects on MPTP-induced oxidative stress in the striatum and brain stem 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), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) 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 brain stem of 3-month-old male Wistar rats given allopurinol (300 mg/kg day by gavage) for 3 days before a single MPTP 35 mg/kg dose IP. Allopurinol alone decreased uric acid and increased xanthine levels both in the striatum and in the brain stem; moreover, allopurinol decreased striatal DOPAC + HVA/DA ratio and increased 5-HIAA/5HT ratio in the brainstem. Allopurinol affected neither regional MPTP nor MPP+ disposition. Allopurinol potentiated the MPTP-induced decrease in the DOPAC+HVA/DA ratio and increase in striatal AA oxidation; in addition, allopurinol antagonised the MPTP-induced: (i) increase in uric acid levels; (ii) decrease in NA levels in both regions, in DA levels, and in the 5-HIAA/5-HT ratio in the brain stem: (iii) increase in AA oxidation in the brain stem. In conclusion, the MPP(+)-induced oxidative stress mediated by xanthine oxidase seems to be involved in DA depletion in the brainstem and in NA depletion in both regions; moreover, striatal uric acid may have an active role in the neuronal antioxidant pool.
authors: Institute of Pharmacology, University of Sassari, Italy.
authors: M S
authors: MS
authors: Desole
authors: G
authors: G
authors: Esposito
authors: L
authors: L
authors: Fresu
authors: R
authors: R
authors: Migheli
authors: S
authors: S
authors: Sircana
authors: R
authors: R
authors: Delogu
authors: M
authors: M
authors: Miele
authors: E
authors: E
authors: Miele
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D019271:Hypoxanthine / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011687:Purines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000378:metabolism
chemical_list: D000963:Antimetabolites; D002395:Catecholamines; D015259:Dopamine Agents; D011687:Purines; D014970:Xanthines; D019271:Hypoxanthine; D000493:Allopurinol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001205:Ascorbic Acid