Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.
Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.
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DOI：
10.1016/s0891-5849(99)00170-7
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发表时间：
1999-11
影响因子：
7.4
通讯作者：
L. Ste-Marie;L. Vachon;C. Bémeur;Jean Lambert;J. Montgomery
中科院分区：
文献类型：
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作者：
L. Ste-Marie;L. Vachon;C. Bémeur;Jean Lambert;J. Montgomery
在大鼠纹状体的体内双边微透析被用来研究基础条件下和纹状体内给药后的神经毒素，1-甲基-4-苯基吡啶（MPP+）的羟基自由基的形成。在短暂的平衡期后，在输注MPP+前15分钟腹膜内注射4-羟基苯甲酸酯（4 HBZ），其清除羟基自由基以产生3，4-二羟基苯甲酸酯（34 DHB）。为了评价酶对羟基自由基形成的贡献，在给予单胺氧化酶B抑制剂1-丙炔苯丙胺（司来吉兰）或MDL 72，974 A [（E）-2-（4-氟苯乙基）-3-氟烯丙胺盐酸盐]后进行另外两个系列的微透析。通过高效液相色谱法分析微透析液样品中的儿茶酚胺、3，4-二羟基苯乙酸盐（DOPAC）、高香草酸盐（HVA）沿着羟基自由基加合物34 DHB及其前体4 HBZ。MPP+给药导致所有三组中多巴胺沿着大量释放，同时DOPAC和HVA降低。在所有三组中均观察到显著效果，其中MPP+导致间质4 HBZ减少至非MPP+处理侧的<50%。就绝对值而言，即使在单侧MPP+输注后，所有三组中产生的34 DHB的量也较低，但相似。当将34 DHB标准化为4 HBZ释放以解释前体可用性的差异时，在有或没有MAO抑制剂治疗或局部MPP+输注后，34 DHB/4 HBZ比率没有显著差异。全身性4 HBZ给药似乎主要导致羟基自由基的细胞内取样，这与局部输注捕获剂（如水杨酸盐）产生不同的结果。
In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). After a short equilibration period, 4-hydroxybenzoate (4HBZ), which scavenges hydroxyl radicals to produce 3,4-dihydroxybenzoate (34DHB), was injected intraperitoneally 15 min before infusion of MPP+. To evaluate the enzymatic contribution to hydroxyl radical formation, two other series of microdialyses were performed following administration of monoamine oxidase B inhibitors, either l-deprenyl (selegiline) or MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride]. Microdialysate samples were analyzed by high-performance liquid chromatography for catecholamines, 3,4-dihydroxyphenylacetate (DOPAC), homovanillate (HVA), along with the hydroxyl radical adduct, 34DHB and its precursor, 4HBZ. MPP+administration resulted in a massive release of dopamine along with a decrease in DOPAC and HVA in all three groups. A striking effect in all three groups was noted in which MPP+resulted in a decrease in interstitial 4HBZ to <50% of the non-MPP+-treated side. In absolute terms, the amount of 34DHB produced was low but similar in all three groups, even after unilateral MPP+infusion. When 34DHB was normalized to 4HBZ release to account for differences in precursor availability, there were no significant differences in the 34DHB/4HBZ ratios either with or without MAO inhibitor treatment or after local MPP+infusion. Systemic 4HBZ administration appears to result predominantly in intra-cellular sampling of hydroxyl radicals which produces different results from local infusion of trapping agents such as salicylate.