Chemical Nanotherapy: Nitroxyl radical-containing Nanoparticle Protects Neuroblastoma SH-SY5Y Cells From Aβ-induced Oxidative Stress

Abstract

Excessive accumulation of beta-amyloid (Abeta) has been proposed as a pivotal event in the pathogenesis of Alzheimer's disease. Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excess production of reactive oxygen species (ROS) and apoptosis. We have designed novel nanoparticles, nitroxyl radical-containing nanoparticles (RNPs), which possess nitroxyl radical in the core and chemically scavenges ROS. This study aimed to determine the potential neuroprotective role of RNPs on Abeta-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were preincubated with 0.1-1 mM RNP for 24 h and then incubated with 20 microM Abeta1-42, for 48 h. In every group, cell viability, apoptotic rate, ROS levels including superoxide anion radicals and hydroxyl radicals, ROS production including lipid peroxidation, protein oxidation and DNA oxidation were measured. SH-SY5Y cells preincubated with 0.1-2 mM RNP for 24 h were protected from Abeta-induced damage. SH-SY5Y cells preincubated with more than 2 mM RNPfor 24 h showed cytotoxicity. From the quantitative analyses, it was observed that RNPs reduced intracellular oxidative stress. RNP treatment significantly reduced the amount of oxidized lipids, proteins and DNA. It also reduced DNA fragmentations, which caused lower apoptosis levels. RNPs are promising intracellular ROS scavengers.