Maharaj D S, Saravanan K S, Maharaj H, Mohanakumar K P, Daya S
Department of Pharmacy, Division of Pharmacology, Rhodes University, PO Box 94, Grahamstown 6140, South Africa.
Neurochem Int. 2004 Apr;44(5):355-60. doi: 10.1016/s0197-0186(03)00170-0.
We assessed the antioxidant activity of non-narcotic analgesics, acetaminophen and aspirin in rat brain homogenates and neuroprotective effects in vivo in rats intranigrally treated with 1-methyl-4-phenyl pyridinium (MPP+). Both drugs inhibited cyanide-induced superoxide anion generation, as well as lipid peroxidation in rat brain homogenates, the combination of the agents resulting in a potentiation of this effect. Acetaminophen or aspirin when administered alone or in combination, did not alter dopamine (DA) levels in the forebrain or in the striatum. Intranigral infusion of MPP+ in rats caused severe depletion of striatal DA levels in the ipsilateral striatum in rats by the third day. Systemic post-treatment of acetaminophen afforded partial protection, whereas similar treatment of aspirin resulted in complete blockade of MPP+-induced striatal DA depletion. While these findings suggest usefulness of non-narcotic analgesics in neuroprotective therapy in neurodegenerative diseases, aspirin appears to be a potential candidate in prophylactic as well as in adjuvant therapy in Parkinson's disease.
我们评估了非麻醉性镇痛药对乙酰氨基酚和阿司匹林在大鼠脑匀浆中的抗氧化活性，以及在经1-甲基-4-苯基吡啶离子（MPP+）脑内注射处理的大鼠体内的神经保护作用。两种药物均抑制了氰化物诱导的大鼠脑匀浆中超氧阴离子的生成以及脂质过氧化，两种药物联合使用可增强此效应。对乙酰氨基酚或阿司匹林单独给药或联合给药时，均未改变前脑或纹状体中的多巴胺（DA）水平。大鼠脑内注射MPP+后，到第三天时，同侧纹状体中的纹状体DA水平严重降低。对乙酰氨基酚全身后处理提供了部分保护作用，而阿司匹林的类似处理则完全阻断了MPP+诱导的纹状体DA耗竭。虽然这些发现表明非麻醉性镇痛药在神经退行性疾病的神经保护治疗中有用，但阿司匹林似乎是帕金森病预防性治疗以及辅助治疗的潜在候选药物。
