Garg Geetika, Singh Sandeep, Singh Abhishek Kumar, Rizvi Syed Ibrahim
Department of Biochemistry, University of Allahabad, Allahabad-211002, India.
Can J Physiol Pharmacol. 2018 Dec;96(12):1189-1196. doi: 10.1139/cjpp-2018-0209. Epub 2018 Aug 14.
N-acetyl-l-cysteine (NAC) is a precursor of cysteine, which is known to increase the level of glutathione (GSH) in the brain. Several neurodegenerative changes linked to oxidative stress take place in the aging brain. This study aimed to assess the neuroprotective effect of NAC supplementation on age-dependent neurodegeneration in the rat brain. Young (4 months) and old (24 months) Wistar rats (n = 6 rats/group) were supplemented with NAC (100 mg/kg b.w. orally) for 14 days. Enzymatic and nonenzymatic antioxidants such as superoxide dismutase and catalase, and GSH and total thiol respectively, prooxidants such as protein carbonyl, advanced oxidation protein products, reactive oxygen species, and malondialdehyde were assessed in the brain homogenates. Furthermore, nitric oxide level, acetylcholinesterase activity, and Na/K-ATPase activity were measured and gene expression studies were also performed. The results indicated that NAC augmented the level of enzymatic and nonenzymatic antioxidants with a significant reduction in prooxidant levels in old rats. NAC supplementation also downregulated the expression of inflammatory markers (TNF-α, IL-1β, IL-6) and upregulated the expression of marker genes associated with aging (sirtuin-1) and neurodegeneration (neuron-specific enolase, neuroglobin, synapsin-I, myelin basic protein 2) in old rats. The present findings support a neuroprotective role of NAC which has therapeutic implication in controlling age-related neurological disorders.
N-乙酰-L-半胱氨酸（NAC）是半胱氨酸的前体，已知其可提高大脑中谷胱甘肽（GSH）的水平。与氧化应激相关的几种神经退行性变化发生在衰老的大脑中。本研究旨在评估补充NAC对大鼠大脑中与年龄相关的神经退行性变的神经保护作用。将年轻（4个月）和老年（24个月）的Wistar大鼠（每组n = 6只大鼠）口服补充NAC（100 mg/kg体重），持续14天。在脑匀浆中评估了酶促和非酶促抗氧化剂，如超氧化物歧化酶和过氧化氢酶，以及GSH和总硫醇，还评估了蛋白质羰基、晚期氧化蛋白产物、活性氧和丙二醛等促氧化剂。此外，测量了一氧化氮水平、乙酰胆碱酯酶活性和Na/K-ATP酶活性，并进行了基因表达研究。结果表明，NAC提高了老年大鼠酶促和非酶促抗氧化剂的水平，同时显著降低了促氧化剂水平。补充NAC还下调了老年大鼠炎症标志物（TNF-α、IL-1β、IL-6）的表达，并上调了与衰老（沉默调节蛋白-1）和神经退行性变（神经元特异性烯醇化酶、神经珠蛋白、突触素-I、髓鞘碱性蛋白2）相关的标志物基因的表达。目前的研究结果支持NAC的神经保护作用，其在控制与年龄相关的神经疾病方面具有治疗意义。
