Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 85, Issue -, Pages 61-70Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2015.06.018
Keywords
Zinc oxide nanoparticles; Cellular uptake; Cytokines; Oxidative stress; Immunotoxicity
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Funding
- Council of Scientific and Industrial Research, New Delhi, India [BSC0112]
- EU [263147]
- Gujarat Institute of Chemical Technology, India under CENTRA (Centre for Nanotechnology and Research Application) project [ILS/GICT/2013/003]
- Council of Scientific and Industrial Research (CSIR), New Delhi
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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-alpha and IL-1 beta) and reactive oxygen species (ROS) was observed with a concomitant concentration dependent (0.5, 1, 5, 10, 15 and 20 mu g/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-kappa B and MAPK signalling pathways. (C) 2015 Elsevier Ltd. All rights reserved.
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