N-Acetylcysteine amide protects against methamphetamine-induced oxidative stress and neurotoxicity in immortalized human brain endothelial cells.
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.
Department of Chemistry, Missouri University of Science and Technology, 400 West 11th Street, 236 Schrenk Hall, Rolla, MO 65409, USA.
Xinsheng
X
Zhang
Atrayee
A
Banerjee
William A
WA
Banks
Nuran
N
Ercal
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D008694:Methamphetamine; C487056:N-Acetylcysteinamide; D000111:Acetylcysteine