Allopurinol protects against manganese-induced oxidative stress in the striatum and in the brainstem of the rat.
Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic acid, glutathione (GSH), noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and and 3-methoxytyramine were determined in the striatum and/or in the brainstem of 3-month-old male Wistar rats given manganese (MnCl2, 200 mg/kg/day for 7 days by gavage) alone or associated with allopurinol. Allopurinol alone (300 mg/kg/day for 4 days by gavage) decreased uric acid and increased xanthine levels both in the striatum and in the brainstem; moreover, allopurinol decreased the striatal DOPAC + HVA/DA ratio. Allopurinol antagonised the Mn-induced: (a) increase in the DOPAC + HVA/DA ratio; (b) increase in uric acid levels and AA oxidation; and (c) decrease in GSH and NA levels. We conclude that allopurinol may protect against Mn-induced oxidative stress by inhibiting both DA oxidative metabolism and xanthine oxidase-mediated formation of reactive oxygen species.
Desole
M S
MS
Institute of Pharmacology, University of Sassari, Italy.
Esposito
G
G
Migheli
R
R
Fresu
L
L
Sircana
S
S
Miele
M
M
De Natale
G
G
Miele
E
E
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000378:metabolism; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
D014970:Xanthines; D019820:Xanthine; D014527:Uric Acid; D008345:Manganese; D000493:Allopurinol; D004298:Dopamine; D009638:Norepinephrine