别嘌醇可保护大鼠纹状体和脑干免受锰诱导的氧化应激。

Allopurinol protects against manganese-induced oxidative stress in the striatum and in the brainstem of the rat.

作者信息

Desole M S, Esposito G, Migheli R, Fresu L, Sircana S, Miele M, De Natale G, Miele E

机构信息

Institute of Pharmacology, University of Sassari, Italy.

出版信息

Neurosci Lett. 1995 Jun 9;192(2):73-6. doi: 10.1016/0304-3940(95)11613-2.

DOI:10.1016/0304-3940(95)11613-2

PMID:7675324

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.

摘要

在单独给予锰（通过灌胃给予200mg/kg/天的MnCl₂，持续7天）或与别嘌呤醇联合给予的3个月大雄性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、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）和3-甲氧基酪胺的水平。单独给予别嘌呤醇（通过灌胃给予300mg/kg/天，持续4天）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，别嘌呤醇降低了纹状体中DOPAC + HVA/DA的比值。别嘌呤醇拮抗锰诱导的：（a）DOPAC + HVA/DA比值升高；（b）尿酸水平升高和AA氧化；以及（c）GSH和NA水平降低。我们得出结论，别嘌呤醇可能通过抑制DA氧化代谢和黄嘌呤氧化酶介导的活性氧形成来预防锰诱导的氧化应激。