Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities,
nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging,
drug delivery and
hyperthermia. Recent studies have shown that
nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of
nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized
nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells.
Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays.
Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of
reactive oxygen species (ROS) and depletion of
antioxidant glutathione (GSH). Further, co-treatment with the
antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to
nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to
nickel ferrite nanoparticles, the level of
mRNA expressions of cell cycle checkpoint
protein p53 and apoptotic
proteins (bax,
caspase-3 and
caspase-9) were significantly up-regulated, whereas the expression of
anti-apoptotic proteins (
survivin and bcl-2) were down-regulated. Moreover, activities of
caspase-3 and
caspase-9 enzymes were also significantly higher in
nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that
nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53,
survivin, bax/bcl-2 and
caspase pathways.