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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Dementia Complex
  • Acetylcysteine / administration & dosage
  • Acetylcysteine / analogs & derivatives*
  • Animals
  • Antioxidants / administration & dosage*
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / pathology
  • Brain / drug effects*
  • Brain / metabolism
  • Glutathione Disulfide / metabolism
  • HIV Envelope Protein gp120 / administration & dosage
  • HIV Infections / drug therapy
  • HIV Infections / metabolism
  • HIV Infections / physiopathology
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity
  • Humans
  • Illicit Drugs / adverse effects
  • Malondialdehyde / metabolism
  • Methamphetamine / administration & dosage
  • Mice
  • Mice, Inbred Strains
  • Oxidative Stress / drug effects
  • Risk Factors
  • Tight Junctions / metabolism
  • tat Gene Products, Human Immunodeficiency Virus / administration & dosage


  • Antioxidants
  • HIV Envelope Protein gp120
  • Illicit Drugs
  • tat Gene Products, Human Immunodeficiency Virus
  • Methamphetamine
  • N-Acetylcysteinamide
  • Malondialdehyde
  • Glutathione Disulfide
  • Acetylcysteine