title: ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach.
abstract: The wide application of zinc oxide nanoparticles (ZnO NPs) in cosmetics, paints, biosensors, drug delivery, food packaging and as anticancerous agents has increased the risk of human exposure to these NPs. Earlier in vitro and in vivo studies have demonstrated a cytotoxic and genotoxic potential of ZnO NPs. However, there is paucity of data regarding their immunomodulatory effects. Therefore, the present study was aimed to investigate the immunotoxic potential of ZnO NPs using human monocytic cell line (THP-1) as model to understand the underlying molecular mechanism. A significant (p < 0.01) increase in pro-inflammatory cytokines (TNF-α and IL-1β) and reactive oxygen species (ROS) was observed with a concomitant concentration dependent (0.5, 1, 5, 10, 15 and 20 μg/mL) decrease in the glutathione (GSH) levels as compared to control. The expression levels of mitogen activated protein kinase (MAPK) cascade proteins such as p-ERK1/2, p-p38 and p-JNK were also significantly (p < 0.05, p < 0.01) induced. Also, at the concentration tested, NPs induced DNA damage as assessed by the Comet and micronucleus assays. Our data demonstrated that ZnO NPs induce oxidative and nitrosative stress in human monocytes, leading to increased inflammatory response via activation of redox sensitive NF-κB and MAPK signalling pathways.
authors.affiliation: Institute of Life Sciences, School of Science and Technology, Ahmedabad University, University Road, Ahmedabad 380009, Gujarat, India; CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Violet Aileen
authors.initials: VA
authors.lastname: Senapati
authors.affiliation: Institute of Life Sciences, School of Science and Technology, Ahmedabad University, University Road, Ahmedabad 380009, Gujarat, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Institute of Life Sciences, School of Science and Technology, Ahmedabad University, University Road, Ahmedabad 380009, Gujarat, India.
authors.forename: Govind Sharan
authors.initials: GS
authors.lastname: Gupta
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow 226001, Uttar Pradesh, India. Electronic address: alokpandey@iitr.res.in.
authors.forename: Alok Kumar
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: Institute of Life Sciences, School of Science and Technology, Ahmedabad University, University Road, Ahmedabad 380009, Gujarat, India; CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow 226001, Uttar Pradesh, India. Electronic address: alok.dhawan@ahduni.edu.in.
authors.forename: Alok
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D065567:Absorption, Physiological; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D004249:DNA Damage; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000633:toxicity*; D053583:Interleukin-1beta / Q000819:agonists / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009569:Nitric Oxide / Q000819:agonists / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D013499:Surface Properties; D018675:Toxicity Tests; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000378:metabolism; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D015415:Biomarkers; C508585:IL1B protein, human; D007155:Immunologic Factors; D053583:Interleukin-1beta; D009153:Mutagens; D017382:Reactive Oxygen Species; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005978:Glutathione; D015034:Zinc Oxide
keywords: Cellular uptake; Cytokines; Immunotoxicity; Oxidative stress; Zinc oxide nanoparticles