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.
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.
Miele
M
M
Institute of Pharmacology, University of Sassari, Italy.
Esposito
G
G
Migheli
R
R
Sircana
S
S
Zangani
D
D
Fresu
G L
GL
Desole
M S
MS
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
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