Further investigation of allopurinol effects on MPTP-induced oxidative stress in the striatum and brain stem of the rat

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1996-06, Vol.54 (2), p.377-383
• Main Authors: Desole, Maria S., Esposito, Giovanni, Fresu, Luigia, Migheli, Rossana, Sircana, Sara, Delogu, Rosaria, Miele, Maddalena, Miele, Egidio
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Allopurinol; Allopurinol - pharmacology; Animals; Antimetabolites - pharmacology; Ascorbic Acid - metabolism; Biological and medical sciences; Brain Stem - drug effects; Brain Stem - metabolism; Catecholamines - metabolism; Dopamine Agents - pharmacology; Hypoxanthine - metabolism; Male; Medical sciences; Miscellaneous; MPTP; Neostriatum - drug effects; Neostriatum - metabolism; Oxidative stress; Oxidative Stress - drug effects; Purines - metabolism; Rats; Rats, Wistar; Striatum Brainstem Rat; Toxicology; Xanthines - metabolism
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(95)02161-2

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.