title: Allopurinol protects against manganese-induced oxidative stress in the striatum and in the brainstem of the rat.
abstract: 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.
authors.affiliation: Institute of Pharmacology, University of Sassari, Italy.
authors.forename: M S
authors.initials: MS
authors.lastname: Desole
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.forename: R
authors.initials: R
authors.lastname: Migheli
authors.forename: L
authors.initials: L
authors.lastname: Fresu
authors.forename: S
authors.initials: S
authors.lastname: Sircana
authors.forename: M
authors.initials: M
authors.lastname: Miele
authors.forename: G
authors.initials: G
authors.lastname: De Natale
authors.forename: E
authors.initials: E
authors.lastname: Miele
mesh_terms: 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
chemical_list: D014970:Xanthines; D019820:Xanthine; D014527:Uric Acid; D008345:Manganese; D000493:Allopurinol; D004298:Dopamine; D009638:Norepinephrine