HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: potential role of the thiol antioxidant N-acetylcysteine amide.
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.
Banerjee
Atrayee
A
Department of Chemistry, Missouri University of Science and Technology, 400 West 11th Street, Rolla, MO 65409, USA.
Zhang
Xinsheng
X
Manda
Kalyan Reddy
KR
Banks
William A
WA
Ercal
Nuran
N
D015526:AIDS Dementia Complex; D000111:Acetylcysteine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects; D008315:Malondialdehyde / Q000378:metabolism; D008694:Methamphetamine / Q000008:administration & dosage; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors; D019108:Tight Junctions / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage
D000975:Antioxidants; D015699:HIV Envelope Protein gp120; D013287:Illicit Drugs; D054322:tat Gene Products, Human Immunodeficiency Virus; D008694:Methamphetamine; C487056:N-Acetylcysteinamide; D008315:Malondialdehyde; D019803:Glutathione Disulfide; D000111:Acetylcysteine