Protective effect of Pycnogenol in human neuroblastoma SH-SY5Y cells following acrolein-induced cytotoxicity.

Protective effect of Pycnogenol in human neuroblastoma SH-SY5Y cells following acrolein-induced cytotoxicity.
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DOI:
10.1016/j.freeradbiomed.2008.08.025
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发表时间:
2008-12-01
影响因子:
7.4
通讯作者:
Scheff, Stephen W.
Scheff, Stephen W.
中科院分区:
医学1区
文献类型:
--
作者:
Ansari, Mubeen A.;Keller, Jeffrey N.;Scheff, Stephen W.

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氧化应激是阿尔茨海默病(Alzheimer's disease,AD)的病因学假说之一。相当多的注意力集中在增加细胞内谷胱甘肽(GSH)水平在许多神经退行性疾病,包括AD。碧萝芷®(PYC)具有抗氧化特性并稳定细胞内抗氧化防御系统,包括谷胱甘肽(GSH)水平。本研究探讨PYC对丙烯醛诱导的SH-SY 5 Y神经母细胞瘤细胞氧化毒性的保护作用。用丙烯醛处理的SH-SY 5 Y培养物中细胞存活率降低与氧化应激、NADPH氧化酶活性增加、自由基产生、蛋白质氧化/硝化(蛋白质羰基、3-硝基酪氨酸)和脂质过氧化(4-羟基-2-壬烯醛)相关。PYC预处理显著减弱丙烯醛诱导的细胞毒性、蛋白质损伤、脂质过氧化和细胞死亡。剂量反应研究表明,PYC通过调节氧化应激和增加GSH对丙烯醛毒性具有保护作用。这些发现支持PYC可能为治疗氧化应激相关的神经退行性疾病(如AD)提供一种有前途的方法。
Oxidative stress is one of the hypotheses involved in the etiology of Alzheimer’s disease (AD). Considerable attention has focused on increasing the intracellular glutathione (GSH) levels in many neurodegenerative diseases, including AD. Pycnogenol® (PYC) has antioxidant properties and stabilizes intracellular antioxidant defense systems including glutathione (GSH) levels. The present study investigated the protective effects of PYC on acrolein-induced oxidative cell toxicity in cultured SH-SY5Y neuroblastoma cells. Decreased cell survival in SH-SY5Y cultures treated with acrolein correlated with oxidative stress, increased NADPH-oxidase activity, free radical production, protein oxidation/nitration (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation (4-hydroxy-2-nonenal). Pretreatment with PYC significantly attenuated acrolein induced cytotoxicity, protein damages, lipid peroxidation, and cell death. A dose-response study suggested that PYC showed protective effects against acrolein toxicity by modulating oxidative stress and increasing GSH. These findings provide support that PYC may provide a promising approach for the treatment of oxidative stress related neurodegenerative diseases such as AD.
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