TY - JOUR
T1 - Further investigation of allopurinol effects on MPTP-induced oxidative stress in the striatum and brain stem of the rat
AU - Desole, Maria S.
AU - Esposito, Giovanni
AU - Fresu, Luigia
AU - Migheli, Rossana
AU - Sircana, Sara
AU - Delogu, Rosaria
AU - Miele, Maddalena
AU - Miele, Egidio
N1 - Funding Information:
The research was supported by MURST (40% quota, Targeted Project “New Assessment Approaches in Toxicology” 1995, and 60% quota, 1995). We are grateful to Prof. G. Grella for synthesis of MPP’ and MPTP-3-01.
PY - 1996/5
Y1 - 1996/5
N2 - 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.
AB - 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.
KW - Allopurinol
KW - Brainstem
KW - MPTP
KW - Oxidative stress
KW - Rat
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=0029894966&partnerID=8YFLogxK
U2 - 10.1016/0091-3057(95)02161-2
DO - 10.1016/0091-3057(95)02161-2
M3 - Article
SN - 0091-3057
VL - 54
SP - 377
EP - 383
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 2
ER -