Comparative evaluation of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) on glutamate and lead-induced toxicity in CD-1 mice
Comparative evaluation of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) on glutamate and lead-induced toxicity in CD-1 mice
复制标题
DOI：
10.1016/j.toxlet.2010.11.013
复制
发表时间：
2011-02-25
影响因子：
3.5
通讯作者：
Ercal, Nuran
中科院分区：
文献类型：
--
作者：
Penugonda, Suman;Ercal, Nuran
近年来的研究表明，谷氨酸能神经递质系统与铅的神经毒性存在相互作用。在此之前，我们已经证明了谷氨酸在铅诱导的PC12细胞死亡中的潜在作用以及新型硫醇抗氧化剂的保护作用。n -乙酰半胱氨酸酰胺（NACA）本研究(1)研究了谷氨酸对铅暴露的CD-1小鼠的潜在影响，(2)评估了NACA对CD-1小鼠谷氨酸和铅毒性的保护作用，(3)将结果与n -乙酰半胱氨酸（一种众所周知的硫醇抗氧化剂）进行了比较。氧化应激参数，包括谷胱甘肽（GSH）、氧化谷胱甘肽（GSSG）、GSH/GSSG和丙二醛（MDA）水平进行评估。还分析了血液和组织铅水平、谷氨酸/谷氨酰胺（Glu/Gln）比率、GS活性和磷脂酶- a (2) （PLA(2)）。结果表明，铅和谷氨酸降低了红细胞、大脑、肝脏和肾脏的谷胱甘肽水平。暴露于谷氨酸和铅会升高丙二醛水平和PLA(2)活性。NACA和n -乙酰半胱氨酸（NAC）通过降低血铅和组织铅水平、恢复细胞内谷胱甘肽水平和降低丙二醛水平来保护小鼠免受铅的有害影响。NACA和NAC也增加了GS活性，从而降低了Glu/Gln水平。然而，由于其更高的亲脂性和穿越血脑屏障的能力，NACA似乎比NAC具有更好的螯合和抗氧化性能。2010爱思唯尔爱尔兰有限公司版权所有。
Recent studies indicate that there is interaction between the glutamatergic neurotransmitters system and lead neurotoxicity. Previously, we have demonstrated the potential effects of glutamate in lead-induced cell death in PC12 cells and the protective role of the novel thiol antioxidant. N-acetylcysteine amide (NACA). The current study (1) investigated the potential effects of glutamate on lead exposed CD-1 mice, (2) evaluated the protective effects of NACA against glutamate and lead toxicity in CD-1 mice, and (3) compared the results with N-aceytylcysteine (a well-known thiol antioxidant). Oxidative stress parameters, including glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, and malondialdehyde (MDA) levels, were evaluated. Blood and tissue lead levels, glutamate/glutamine (Glu/Gln) ratios, GS activity, and phospholipase-A(2) (PLA(2)) were also analyzed. Results indicated that lead and glutamate decreased GSH levels in the red blood cells, brains, livers, and kidneys. Exposure to glutamate and lead elevated the MDA levels and PLA(2) activity. NACA and N-acetylcysteine (NAC) provided protection against the detrimental effects of lead by decreasing the blood and tissue lead levels, restoring intracellular GSH levels, and decreasing the MDA levels. NACA and NAC also increased the GS activity thereby decreasing Glu/Gln levels. However, NACA appeared to have better chelating and antioxidant properties than NAC, due to its higher liphophilicity and its ability to cross the blood-brain barrier. (C) 2010 Elsevier Ireland Ltd. All rights reserved.