Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain
Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain
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DOI：
10.1016/s0006-8993(97)01521-7
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发表时间：
1998-04-20
期刊：
影响因子：
2.9
通讯作者：
Ogawa, N
中科院分区：
文献类型：
--
作者：
Gómez-Vargas, M;Nishibayashi-Asanuma, S;Ogawa, N
近年来，关于帕金森病(PD)发病机制和/或进展的自由基假说得到了广泛的认可。虽然很明显，多巴胺(DA)激动剂不能完全取代左旋多巴疗法，但它们在帕金森病早期可以通过减少DA的积累而受益，DA经历自动氧化并产生细胞毒性自由基。在目前的研究中，我们证明了广泛使用的DA激动剂培高利特具有清除自由基和抗氧化活性。使用一氧化氮自由基直接检测系统(No.)通过电子自旋共振(ESR)谱在体外。NO生成系统中，我们考察了培高利特对NO生成的猝灭作用。已生成。培高利特以剂量依赖方式清除NO.在竞争试验中，培高利特的IC50值约为30mU。在体外FeSO4-H_2O_2 ESR体系中，培高利特也呈剂量依赖性地减弱羟基自由基(OH)信号，IC50值约为300mM。此外，在体外实验和重复给药(0.5 mg/kg/24 h，i.p)后，该药显著抑制大鼠脑匀浆的磷脂过氧化。7天)。我们的发现表明，培高利特通过清除自由基和抗氧化特性，对多巴胺能神经元起到神经保护作用。(C)1998年爱思唯尔科学公司。
The free radical hypothesis for the pathogenesis and/or progression of Parkinson's disease (PD) has gained wide acceptance in recent years. Although it is clear that dopamine (DA) agonists cannot completely replace levodopa therapy, they can be beneficial early in the course of PD by reducing the accumulation of DA which undergoes auto-oxidation and generates cytotoxic free radicals. In the present study we demonstrate that pergolide, a widely used DA agonist, has free radical scavenging and antioxidant activities. Using a direct detection system for nitric oxide radical (NO .) by electron spin resonance (ESR) spectrometry in an in vitro . NO-generating system, we examined the quenching effects of pergolide on the amount of NO . generated. Pergolide dose-dependently scavenged NO .. In the competition assay, the IC50 value for pergolide was estimated to be about 30 mu M. Pergolide also dose-dependently attenuated the hydroxyl radical(OH) signal in an in vitro FeSO4-H2O2 ESR system with an approximate IC50 value of 300 mu M. Furthermore, this agent significantly inhibited phospholipid peroxidation of rat brain homogenates in in vitro experiments and after repeated administration (0.5 mg/kg/24 h, i.p. for 7 days). Our findings suggest a neuroprotective role for pergolide on dopaminergic neurons due to its free radical scavenging and antioxidant properties. (C) 1998 Elsevier Science B.V.