Salicylic acid protects against chronic l-DOPA-induced 6-OHDA generation in experimental model of parkinsonism
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- 作者：Anupom Borah ; Kochupurackal P. Mohanakumar
- 关键词：MPTP ; Reactive oxygen species ; Dopamine oxidation product ; Hydroxyl radical ; Neuroprotection ; Median forebrain bundle ; Parkinson's disease ; Dopamine quinones ; Neurodegeneration ; l-DOPA toxicity
- 刊名：Brain Research
- 出版年：2010
- 出版时间：16 July 2010
- 年：2010
- 卷：1344
- 期：Complete
- 页码：192-199
- 全文大小：426 K
文摘
The present study evaluated the ability of salicylic acid (SA) to attenuate long-term l-DOPA-induced 6-hydroxydopamine (6-OHDA) formation in the striatum of mice, and to protect against the resulting dopaminergic neurotoxicity. The production of 6-OHDA from dopamine in vitro from ferrous-ascorbate-dopamine (FAD) hydroxyl radical (•OH) generating system or in vivo in the striatum following prolonged administration of l-DOPA in mice were found to be significantly attenuated by SA. Intra-median forebrain bundle infusion of FAD, but not equivalent dose of ferrous ion or dopamine individually, caused significant striatal dopamine depletion, which was blocked by SA administration. The dose- and time-dependent increase in the formation of 6-OHDA following l-DOPA treatment in the mouse striatum was synergistically enhanced to the systemic administration of the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. SA treatment significantly attenuated the l-DOPA plus the parkinsonian neurotoxin-induced striatal 6-OHDA generation, and protected against striatal dopamine loss. The present study demonstrated a novel mode of dopaminergic neuroprotection by SA and its possible therapeutic implication in the treatment of Parkinson's disease.