Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells

• Published in: Toxicology (Amsterdam) Vol. 283; no. 2; pp. 101 - 108
• Main Authors: Ahamed, Maqusood, Akhtar, Mohd Javed, Siddiqui, Maqsood A, Ahmad, Javed, Musarrat, Javed, Al-Khedhairy, Abdulaziz A, AlSalhi, Mohamad S, Alrokayan, Salman A
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 10-05-2011; Elsevier
• Subjects: antioxidants; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Biological and medical sciences; Caspase 3 - metabolism; Caspase 9 - metabolism; caspase-3; caspase-9; cell cycle; Cell Death - drug effects; Cell Line; Chemical and industrial products toxicology. Toxic occupational diseases; Coloring Agents; cytotoxicity; drugs; electrical properties; Emergency; Ferric Compounds - toxicity; fever; gene expression; gene expression regulation; glutathione; Glutathione - metabolism; Humans; Indicators and Reagents; Inhibitor of Apoptosis Proteins - metabolism; L-Lactate Dehydrogenase - metabolism; magnetic resonance imaging; Medical sciences; messenger RNA; Metals and various inorganic compounds; Nanoparticles; Neutral Red; nickel; Nickel - toxicity; Nickel ferrite nanoparticles; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; p53; proteins; quantitative polymerase chain reaction; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - isolation & purification; Survivin; Tetrazolium Salts; Thiazoles; Toxicology; X-Ray Diffraction; Oxidative stress; Nickel ferrite nanoparticles; Survivin; Apoptosis; p53; Human; Nanoparticle; Lung; Transition metal; Ultrafine particle; Respiratory system; In vitro; Cell line; TP53 Gene; Apoptosis inhibitory protein; Cell death; Nickel; Tumor suppressor gene
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2011.02.010

Abstract 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.