Miele M, Esposito G, Migheli R, Sircana S, Zangani D, Fresu G L, Desole M S
Institute of Pharmacology, University of Sassari, Italy.
Neurosci Lett. 1995 Jan 9;183(3):155-9. doi: 10.1016/0304-3940(94)11138-9.
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.
在3个月大的雄性Wistar大鼠的纹状体和/或脑干中测定尿酸、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）、1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和1-甲基-4-苯基吡啶离子（MPP+）的水平。在腹腔注射单次52 mg/kg剂量的MPTP前3天，给大鼠灌胃给予别嘌呤醇（500 mg/kg/天）。单独使用别嘌呤醇可降低纹状体和脑干中的尿酸和次黄嘌呤水平；此外，别嘌呤醇增加了AA氧化并降低了纹状体DA代谢产物。别嘌呤醇既不影响区域MPTP和MPP+水平，也不影响MPTP诱导的纹状体DA氧化代谢抑制。相反，MPTP诱导的尿酸水平升高以及黄嘌呤、次黄嘌呤和NA水平降低被完全拮抗。这些发现表明，所声称的由黄嘌呤氧化酶介导的MPP(+)诱导的氧化应激可能至少参与了NA耗竭；此外，尿酸可能作为神经元抗氧化池的活性成分具有生理作用。
