N-Acetylcysteine Amide Protects Against Methamphetamine-induced Oxidative Stress and Neurotoxicity in Immortalized Human Brain Endothelial Cells
Abstract
Oxidative stress plays an important role in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Methamphetamine (METH) is an amphetamine analog that causes degeneration of the dopaminergic system in mammals and subsequent oxidative stress. In our present study, we have used immortalized human brain microvascular endothelial (HBMVEC) cells to test whether N-acetylcysteine amide (NACA), a novel antioxidant, prevents METH-induced oxidative stress in vitro. Our studies showed that NACA protects against METH-induced oxidative stress in HBMVEC cells. NACA significantly protected the integrity of our blood brain barrier (BBB) model, as shown by permeability and trans-endothelial electrical resistance (TEER) studies. NACA also significantly increased the levels of intracellular glutathione (GSH) and glutathione peroxidase (GPx). Malondialdehyde (MDA) levels increased dramatically after METH exposure, but this increase was almost completely prevented when the cells were treated with NACA. Generation of reactive oxygen species (ROS) also increased after METH exposure, but was reduced to control levels with NACA treatment, as measured by dichlorofluorescin (DCF). These results suggest that NACA protects the BBB integrity in vitro, which could prevent oxidative stress-induced damage; therefore, the effectiveness of this antioxidant should be evaluated for the treatment of neurodegenerative diseases in the future.
Recommended Citation
N. Ercal et al., "N-Acetylcysteine Amide Protects Against Methamphetamine-induced Oxidative Stress and Neurotoxicity in Immortalized Human Brain Endothelial Cells," Brain Research, Elsevier, Jun 2009.
The definitive version is available at https://doi.org/10.1016/j.brainres.2009.04.008
Department(s)
Chemistry
International Standard Serial Number (ISSN)
0006-8993
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2009 Elsevier, All rights reserved.
Publication Date
01 Jun 2009