Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice
Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice
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DOI：
10.1046/j.1471-4159.1998.71041635.x
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发表时间：
1998-10-01
影响因子：
4.7
通讯作者：
Carter, C
中科院分区：
文献类型：
--
作者：
Aubin, N;Curet, O;Carter, C
多巴胺选择性神经毒素MPTP（15 mg/kg，s，c.）的神经毒性作用，在小鼠中，通过全身施用水杨酸盐（ED 50 = 40 mg/kg，i，p.）阿司匹林（ED 50 = 60 mg/kg，腹膜内），或阿司匹林的可溶性赖氨酸盐Aspegic（ED 50 = 80 mg/kg，腹膜内）。阿司匹林的保护作用不太可能与对乙酰氨基酚（100 mg/kg，腹腔注射）的环氧合酶抑制作用有关，双氯芬酸（100 mg/kg，i. p.）、布洛芬（20 mg/kg，i. p.）和吲哚美辛（100 mg/kg，i. p.）是无效的。地塞米松（3-30 mg/kg，i，p.），其与阿司匹林和水杨酸盐一样，已被报道抑制转录因子NF-κ β，也是无效的。阿司匹林或水杨酸盐（100 μ M）对纹状体突触体的多巴胺摄取或单胺氧化酶B活性没有影响。水杨酸衍生物的神经保护作用可能与清除羟自由基有关。这是由以下事实表明，水杨酸酯（2，3-和2，5-二氢苯甲酸）的羟基化代谢产物在MPTP和阿司匹林联合给药后在脑组织中的回收程度大于单独服用阿司匹林。阿司匹林在帕金森病动物模型中令人惊讶的神经保护作用值得进一步的临床研究。
The neurotoxic effects of the dopamine-selective neurotoxin MPTP(15 mg/kg, s,c.), in mice, were totally prevented by systemic administration of salicylate (ED50 = 40 mg/kg, i,p.), aspirin (ED50 = 60 mg/kg, i.p.), or the soluble lysine salt of aspirin, Aspegic (ED50 = 80 mg/kg, i.p.). The protective effects of aspirin are unlikely to be related to cyclooxygenase inhibition as paracetamol(100 mg/kg, i.p.),diclofenac (100 mg/kg, i.p,), ibuprofen (20 mg/kg, i.p.) and indomethacin (100 mg/kg, i.p.) were ineffective. Dexamethasone (3-30 mg/kg, i,p.),which, like aspirin and salicylate, has: been reported to inhibit the transcription factor NF-kappa beta, was also ineffective. Aspirin or salicylate (100 mu M) had no effect on dopamine uptake into striatal synaptosomes or on monoamine oxidase B activity. The neuroprotective effects of salicylate derivatives could perhaps be related to hydroxyl radical scavenging. This was suggested by the fact that hydroxylated metabolites of salicylate (2,3- and 2,5-dihydrobenzoic acid) were recovered in brain tissue following the combined administration of MPTP and aspirin to a greater extent than following aspirin alone. The surprising neuroprotective effects of aspirin in an animal model of Parkinson's disease warrant further clinical investigation.