MgO nanoparticles cytotoxicity caused primarily by GSH depletion in human lung epithelial cells

Abstract

Bio-response of magnesium oxide nanoparticles (MgO NPs) is emerging, obviously, with a conflicting flavor. This study evaluates the underlying mechanism of bio-responses of MgO NPs in human lung epithelial (A549) cell. TEM size of NPs was 40-50 nm and cuboidal in shape. EDS data showed no detectable impurity. Zeta potential of MgO NPs suggested a fair dispersion in complete culture media and in PBS. MgO NPs induced a concentration dependent cytotoxicity when measured by MTT and NRU. MgO NPs induced cytotoxicity strongly correlated with intracellular depletion of antioxidant GSH. MgO NPs did not induce concentration dependent ROS. All live treatment conditions caused autophagy, a survival mechanism when deprived of nutrients and antioxidant. At highest cytotoxic concentration of MgO NPs, there was significant elevation in MMP and caspase-3 activity. GSH depletion mediated autophagy failure lead to MgO NPs induced death at higher concentrations that might have potentiated by induced ROS. This study suggested a mechanism of cytotoxicity caused by MgO NPs that was primarily dependent on GSH depletion, and ROS induction played secondary role in toxicity. Significantly higher toxicity observed for MgO NPs in comparison to Mg salt clearly indicated the involvement of nanoparticulate form in toxicity.

Keywords: Autophagosome; Caspase-3 activity; Cytotoxicity; MgO NPs; ROS-independent.