Department of Chemistry, Missouri University of Science and Technology, 400 West 11th Street, Rolla, MO 65409, USA.
Free Radic Biol Med. 2010 May 15;48(10):1388-98. doi: 10.1016/j.freeradbiomed.2010.02.023. Epub 2010 Feb 24.
An increased risk of HIV-1 associated dementia (HAD) has been observed in patients abusing methamphetamine (METH). Since both HIV viral proteins (gp120, Tat) and METH induce oxidative stress, drug abusing patients are at a greater risk of oxidative stress-induced damage. The objective of this study was to determine if N-acetylcysteine amide (NACA) protects the blood brain barrier (BBB) from oxidative stress-induced damage in animals exposed to gp120, Tat and METH. To study this, CD-1 mice pre-treated with NACA/saline, received injections of gp120, Tat, gp120+Tat or saline for 5days, followed by three injections of METH/saline on the fifth day, and sacrificed 24h after the final injection. Various oxidative stress parameters were measured, and animals treated with gp120+Tat+Meth were found to be the most challenged group, as indicated by their GSH and MDA levels. Treatment with NACA significantly rescued the animals from oxidative stress. Further, NACA-treated animals had significantly higher expression of TJ proteins and BBB permeability as compared to the group treated with gp120+Tat+METH alone, indicating that NACA can protect the BBB from oxidative stress-induced damage in gp120, Tat and METH exposed animals, and thus could be a viable therapeutic option for patients with HAD.
滥用 methamphetamine（METH）的患者中观察到 HIV-1 相关痴呆（HAD）的风险增加。由于 HIV 病毒蛋白（gp120、Tat）和 METH 都会引起氧化应激，因此滥用药物的患者更容易受到氧化应激引起的损伤。本研究的目的是确定 N-乙酰半胱氨酸酰胺（NACA）是否可以保护血脑屏障（BBB）免受暴露于 gp120、Tat 和 METH 的动物的氧化应激损伤。为了进行这项研究，用 NACA/生理盐水预处理 CD-1 小鼠，然后接受 gp120、Tat、gp120+Tat 或生理盐水注射 5 天，然后在第 5 天接受三次 METH/生理盐水注射，并在最后一次注射后 24 小时处死。测量了各种氧化应激参数，结果表明，用 gp120+Tat+Meth 处理的动物是最具挑战性的一组，这反映在它们的 GSH 和 MDA 水平上。用 NACA 治疗可显著使动物免受氧化应激的影响。此外，与仅用 gp120+Tat+METH 处理的组相比，用 NACA 处理的动物 TJ 蛋白和 BBB 通透性的表达明显更高，表明 NACA 可以保护 BBB 免受 gp120、Tat 和 METH 暴露动物的氧化应激损伤，因此可能是 HAD 患者的一种可行的治疗选择。
