HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: potential role of the thiol antioxidant N-acetylcysteine amide.

Author(s): Banerjee A, Zhang X, Manda KR, Banks WA, Ercal N

Affiliation(s): Department of Chemistry, Missouri University of Science and Technology, 400 West 11th Street, Rolla, MO 65409, USA.

Publication date & source: 2010-05-15, Free Radic Biol Med., 48(10):1388-98. Epub 2010 Feb 24.

Publication type: Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

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. Copyright 2010 Elsevier Inc. All rights reserved.