Further investigation of allopurinol effects on MPTP-induced oxidative stress in the striatum and 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), 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.
Desole
M S
MS
Institute of Pharmacology, University of Sassari, Italy.
Esposito
G
G
Fresu
L
L
Migheli
R
R
Sircana
S
S
Delogu
R
R
Miele
M
M
Miele
E
E
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
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