Silica-Coated Superparamagnetic Iron Oxide Nanoparticles Ameliorate Leukoaraiosis-Triggered Oxidative Stress via Targeting of Nrf2 to Activate IRS-1/Akt Signals

Abstract

This study mainly explored the amelioratory effect of silica-coated superparamagnetic iron oxide nanoparticles (SiO4@SPIONs) on leukoaraiosis-associated cognitive dysfunction via targeting of Nrf2 and their potential mechanism. PC12 cell line was given in vitro hypoxia-reoxygenation treatment (OGD/R) and divided into normal group, model group and SiO4@SPIONs treatment group. The cell survival rate, apoptosis rate, levels of ROS (reactive oxygen species), MDA (Malondialdehyde; malonic dialdehyde; Propanedial) and anti-oxidases were monitored. Western-blotting measured the level of Akt and Nrf2. The Akt-targeting antagonist LY294002 was applied for verifying the regulatory effect of SiO4@SPIONs. In comparison with normal cells, model cells exhibited significantly reduced viability, along with significantly elevated apoptosis rate. Meanwhile, model cells also displayed elevated levels of intracellular ROS and MDA, with diminished levels of SOD (Superoxide Dismutase), GSH (glutathione), CAT (Computerized Axial Tomography) and GSH-Px (glutathione peroxidase) which were accompanied by significantly weakened phosphorylation level of Akt. Lastly, model cells also exhibited moderate enhancement of Nrf2 and HO-1 expressions. Moreover, cells in SiO4@SPIONs treatment group exhibited significantly increased viability, along with reduced apoptosis rate. Meanwhile, the cells in the SiO4@SPIONs treatment group also displayed decreased levels of intracellular ROS and MDA, while showing increased levels of SOD, GSH, CAT and GSH-Px, which were accompanied by significantly increased Akt phosphorylation and Nrf2 and HO-1 expressions. The SiO4@SPIONS can ameliorate the leukoaraiosis-triggered oxidative stress via targeting of Nrf2 to activate the IRS-1/Akt signals.