Desole M S, Esposito G, Fresu L, Migheli R, Sircana S, Delogu R, Miele M, Miele E
Institute of Pharmacology, University of Sassari, Italy.
Pharmacol Biochem Behav. 1996 Jun;54(2):377-83. doi: 10.1016/0091-3057(95)02161-2.
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.
在3月龄雄性Wistar大鼠腹腔注射35mg/kg单剂量1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）前3天，通过灌胃给予其别嘌呤醇（300mg/kg/天），之后测定纹状体和/或脑干中尿酸、黄嘌呤、次黄嘌呤、抗坏血酸（AA）、脱氢抗坏血酸（DHAA）、谷胱甘肽（GSH）、去甲肾上腺素（NA）、多巴胺（DA）、二羟基苯乙酸（DOPAC）、高香草酸（HVA）、5-羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）、1-甲基-4-苯基吡啶离子（MPP+）的水平。单独使用别嘌呤醇可降低纹状体和脑干中的尿酸水平并升高黄嘌呤水平；此外，别嘌呤醇可降低纹状体中DOPAC+HVA/DA比值，并升高脑干中5-HIAA/5-HT比值。别嘌呤醇对区域MPTP和MPP+的分布均无影响。别嘌呤醇增强了MPTP诱导的DOPAC+HVA/DA比值降低以及纹状体中AA氧化增加；此外，别嘌呤醇拮抗了MPTP诱导的：（i）尿酸水平升高；（ii）两个区域的NA水平、DA水平以及脑干中5-HIAA/5-HT比值降低；（iii）脑干中AA氧化增加。总之，由黄嘌呤氧化酶介导的MPP(+)诱导的氧化应激似乎参与了脑干中DA的耗竭以及两个区域中NA的耗竭；此外，纹状体尿酸可能在神经元抗氧化池中发挥积极作用。
