HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: potential role of the thiol antioxidant N-acetylcysteine amide.
HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: potential role of the thiol antioxidant N-acetylcysteine amide.
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DOI：
10.1016/j.freeradbiomed.2010.02.023
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发表时间：
2010-05-15
影响因子：
7.4
通讯作者：
Ercal, Nuran
中科院分区：
文献类型：
--
作者：
Banerjee, Atrayee;Zhang, Xinsheng;Manda, Kalyan Reddy;Banks, William A.;Ercal, Nuran
在滥用甲基苯丙胺（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（gp 120、达特）和METH均诱导氧化应激，药物滥用患者发生氧化应激诱导损伤的风险更大。本研究的目的是确定N-乙酰半胱氨酸酰胺（NACA）是否保护暴露于gp 120，达特和METH的动物的血脑屏障（BBB）免受氧化应激诱导的损伤。为了研究这一点，用NACA/盐水预处理的CD-1小鼠接受gp 120、达特、gp 120+达特或盐水注射5天，然后在第5天注射三次METH/盐水，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，发现用gp 120+达特+甲基处理的动物是最受攻击的组，如它们的GSH和MDA水平所示。NACA治疗显着使动物免受氧化应激。此外，与单独用gp 120+达特+METH处理的组相比，NACA处理的动物具有显著更高的TJ蛋白表达和BBB渗透性，表明NACA可以保护BBB免受gp 120、达特和METH暴露的动物中的氧化应激诱导的损伤，并且因此可以是患有HAD的患者的可行的治疗选择。
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 5 days, followed by three injections of METH/saline on the fifth day, and sacrificed 24 h 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.
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