Jesudason E Philip, Masilamoni J Gunasingh, Jesudoss K Samuel, Jayakumar R
Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai, India.
Mol Cell Biochem. 2005 Feb;270(1-2):29-37. doi: 10.1007/s11010-005-3301-z.
Recent reports indicate that beta-amyloid peptide (Abeta) vaccine based therapy for Alzheimer's disease (AD) may be on the horizon. There are however, concerns about the safety of this approach. Immunization with Abeta has several disadvantages, because it crosses the blood brain barrier and cause inflammation and neurotoxicity. The present work is aimed to study the protective effective of alpha-lipoic acid (LA) in the oxidative vulnerability of beta-amyloid in plasma, liver, spleen and brain, when Abeta fibrils are given intraperitoneally in inflammation induced mice. Result shows that reactive oxygen species (ROS) in the astrocytes of inflammation induced mice along with Abeta (IA) has shown 2.5-fold increase when compared with LA treated mice. The increased level of lipid peroxidase (LPO) (p < 0.05) and decreased antioxidant status (p < 0.05) were observed in the plasma, liver, spleen and brain of LA induced mice when compared with LA treated mice. Data shows that there were no significant changes observed between the control and LA treated mice. Our biochemical and histological results highlight that significant oxidative vulnerability was observed in IA treated mice, which was prevented by LA therapy. Our findings suggest that the antioxidant effect of LA when induced with Abeta may serve as a potent therapeutic tool for inflammatory AD models.
近期报告表明,基于β-淀粉样肽(Aβ)疫苗的阿尔茨海默病(AD)治疗方法可能即将出现。然而,人们对这种方法的安全性存在担忧。用Aβ进行免疫有几个缺点,因为它会穿过血脑屏障并引起炎症和神经毒性。目前的工作旨在研究在给炎症诱导小鼠腹腔注射Aβ原纤维时,α-硫辛酸(LA)对血浆、肝脏、脾脏和大脑中β-淀粉样蛋白氧化易损性的保护作用。结果显示,与LA处理的小鼠相比,炎症诱导小鼠(IA)的星形胶质细胞中的活性氧(ROS)增加了2.5倍。与LA处理的小鼠相比,在LA诱导小鼠的血浆、肝脏、脾脏和大脑中观察到脂质过氧化酶(LPO)水平升高(p < 0.05)和抗氧化状态降低(p < 0.05)。数据表明,在对照小鼠和LA处理的小鼠之间未观察到显著变化。我们的生化和组织学结果突出表明,在IA处理的小鼠中观察到显著的氧化易损性,而LA治疗可预防这种情况。我们的研究结果表明,LA与Aβ一起诱导时的抗氧化作用可能成为炎症性AD模型的有效治疗工具。