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ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach
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...
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| Published in: | Food and chemical toxicology 2015-11, Vol.85, p.61-70 |
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| creator | Senapati, Violet Aileen Kumar, Ashutosh Gupta, Govind Sharan Pandey, Alok Kumar Dhawan, Alok |
| description | 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 |
| doi_str_mv | 10.1016/j.fct.2015.06.018 |
| format | article |
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[Display omitted]
•ZnO NPs are widely used in cosmetics, food packaging, medicine etc but their unique properties cause deleterious health effects.•This study was performed to evaluate the immunomodulatory and genotoxic effect of ZnO NPs in human monocytic cell (THP-1).•ZnO NPs exposure to THP-1 cells leads to the release of pro-inflammatory cytokines with increase in oxidative and nitrosative stress.•ZnO NPs induced activation of NF-κB and MAPK signalling pathway.•There is a need to implement guidelines for NPs usage in consumer goods.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2015.06.018</identifier><identifier>PMID: 26146191</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Absorption, Physiological ; Biomarkers - chemistry ; Biomarkers - metabolism ; Cell Line ; Cellular uptake ; Cytokines ; DNA Damage ; Glutathione - antagonists & inhibitors ; Glutathione - metabolism ; Humans ; Immunologic Factors - chemistry ; Immunologic Factors - toxicity ; Immunotoxicity ; Interleukin-1beta - agonists ; Interleukin-1beta - metabolism ; MAP Kinase Signaling System - drug effects ; Metal Nanoparticles - toxicity ; Metal Nanoparticles - ultrastructure ; Monocytes - drug effects ; Monocytes - immunology ; Monocytes - metabolism ; Monocytes - ultrastructure ; Mutagens - chemistry ; Mutagens - toxicity ; Nitric Oxide - agonists ; Nitric Oxide - metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Particle Size ; Reactive Oxygen Species - agonists ; Reactive Oxygen Species - metabolism ; Surface Properties ; Toxicity Tests ; Tumor Necrosis Factor-alpha - agonists ; Tumor Necrosis Factor-alpha - metabolism ; Zinc Oxide - chemistry ; Zinc Oxide - toxicity ; Zinc oxide nanoparticles</subject><ispartof>Food and chemical toxicology, 2015-11, Vol.85, p.61-70</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-35c803f9f4d81b3283855bb4712d18bc8f84299fa6a2ec548a4a3d06204a40ec3</citedby><cites>FETCH-LOGICAL-c522t-35c803f9f4d81b3283855bb4712d18bc8f84299fa6a2ec548a4a3d06204a40ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26146191$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Senapati, Violet Aileen</creatorcontrib><creatorcontrib>Kumar, Ashutosh</creatorcontrib><creatorcontrib>Gupta, Govind Sharan</creatorcontrib><creatorcontrib>Pandey, Alok Kumar</creatorcontrib><creatorcontrib>Dhawan, Alok</creatorcontrib><title>ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>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.
[Display omitted]
•ZnO NPs are widely used in cosmetics, food packaging, medicine etc but their unique properties cause deleterious health effects.•This study was performed to evaluate the immunomodulatory and genotoxic effect of ZnO NPs in human monocytic cell (THP-1).•ZnO NPs exposure to THP-1 cells leads to the release of pro-inflammatory cytokines with increase in oxidative and nitrosative stress.•ZnO NPs induced activation of NF-κB and MAPK signalling pathway.•There is a need to implement guidelines for NPs usage in consumer goods.</description><subject>Absorption, Physiological</subject><subject>Biomarkers - chemistry</subject><subject>Biomarkers - metabolism</subject><subject>Cell Line</subject><subject>Cellular uptake</subject><subject>Cytokines</subject><subject>DNA Damage</subject><subject>Glutathione - antagonists & inhibitors</subject><subject>Glutathione - metabolism</subject><subject>Humans</subject><subject>Immunologic Factors - chemistry</subject><subject>Immunologic Factors - toxicity</subject><subject>Immunotoxicity</subject><subject>Interleukin-1beta - agonists</subject><subject>Interleukin-1beta - metabolism</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Metal Nanoparticles - toxicity</subject><subject>Metal Nanoparticles - ultrastructure</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - immunology</subject><subject>Monocytes - metabolism</subject><subject>Monocytes - ultrastructure</subject><subject>Mutagens - chemistry</subject><subject>Mutagens - toxicity</subject><subject>Nitric Oxide - agonists</subject><subject>Nitric Oxide - metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Particle Size</subject><subject>Reactive Oxygen Species - agonists</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Surface Properties</subject><subject>Toxicity Tests</subject><subject>Tumor Necrosis Factor-alpha - agonists</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Zinc Oxide - chemistry</subject><subject>Zinc Oxide - toxicity</subject><subject>Zinc oxide nanoparticles</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQQC1ERZfCD-CCfOSS1OOvOHCqqhaQKvUCFy6WYzusV4kd7ASx_x6vtnCE01zevLH8EHoDpAUC8vrQjnZtKQHREtkSUM_QDlTHGskEPEc7QjvVyB7EJXpZyoEQ0kEnX6BLKoFL6GGH5m_xEUcT02LyGuzkCw7Rbda7OsfJzLNZUz7i7MuSYvHYRIe_-5jW9CvYsB4rhvfbbCIeppQctn6aynt8g2dv9yaGUq3YLEtOxu5foYvRTMW_fppX6Ov93ZfbT83D48fPtzcPjRWUrg0TVhE29iN3CgZGFVNCDAPvgDpQg1Wj4rTvRyMN9VZwZbhhjkhKuOHEW3aF3p299eyPzZdVz6GcXmaiT1vR0AmgRIlq_j_KJAfZgawonFGbUynZj3rJYTb5qIHoUxB90DWIPgXRROoapO68fdJvw-zd340_BSrw4Qz4-h8_g8-62OBjDRCyrzKXwj_0vwGnfZwr</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Senapati, Violet Aileen</creator><creator>Kumar, Ashutosh</creator><creator>Gupta, Govind Sharan</creator><creator>Pandey, Alok Kumar</creator><creator>Dhawan, Alok</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20151101</creationdate><title>ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach</title><author>Senapati, Violet Aileen ; Kumar, Ashutosh ; Gupta, Govind Sharan ; Pandey, Alok Kumar ; Dhawan, Alok</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-35c803f9f4d81b3283855bb4712d18bc8f84299fa6a2ec548a4a3d06204a40ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Absorption, Physiological</topic><topic>Biomarkers - chemistry</topic><topic>Biomarkers - metabolism</topic><topic>Cell Line</topic><topic>Cellular uptake</topic><topic>Cytokines</topic><topic>DNA Damage</topic><topic>Glutathione - antagonists & inhibitors</topic><topic>Glutathione - metabolism</topic><topic>Humans</topic><topic>Immunologic Factors - chemistry</topic><topic>Immunologic Factors - toxicity</topic><topic>Immunotoxicity</topic><topic>Interleukin-1beta - agonists</topic><topic>Interleukin-1beta - metabolism</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Metal Nanoparticles - toxicity</topic><topic>Metal Nanoparticles - ultrastructure</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - immunology</topic><topic>Monocytes - metabolism</topic><topic>Monocytes - ultrastructure</topic><topic>Mutagens - chemistry</topic><topic>Mutagens - toxicity</topic><topic>Nitric Oxide - agonists</topic><topic>Nitric Oxide - metabolism</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Particle Size</topic><topic>Reactive Oxygen Species - agonists</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Surface Properties</topic><topic>Toxicity Tests</topic><topic>Tumor Necrosis Factor-alpha - agonists</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Zinc Oxide - chemistry</topic><topic>Zinc Oxide - toxicity</topic><topic>Zinc oxide nanoparticles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Senapati, Violet Aileen</creatorcontrib><creatorcontrib>Kumar, Ashutosh</creatorcontrib><creatorcontrib>Gupta, Govind Sharan</creatorcontrib><creatorcontrib>Pandey, Alok Kumar</creatorcontrib><creatorcontrib>Dhawan, Alok</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Senapati, Violet Aileen</au><au>Kumar, Ashutosh</au><au>Gupta, Govind Sharan</au><au>Pandey, Alok Kumar</au><au>Dhawan, Alok</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2015-11-01</date><risdate>2015</risdate><volume>85</volume><spage>61</spage><epage>70</epage><pages>61-70</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><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.
[Display omitted]
•ZnO NPs are widely used in cosmetics, food packaging, medicine etc but their unique properties cause deleterious health effects.•This study was performed to evaluate the immunomodulatory and genotoxic effect of ZnO NPs in human monocytic cell (THP-1).•ZnO NPs exposure to THP-1 cells leads to the release of pro-inflammatory cytokines with increase in oxidative and nitrosative stress.•ZnO NPs induced activation of NF-κB and MAPK signalling pathway.•There is a need to implement guidelines for NPs usage in consumer goods.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26146191</pmid><doi>10.1016/j.fct.2015.06.018</doi><tpages>10</tpages></addata></record> |
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| ispartof | Food and chemical toxicology, 2015-11, Vol.85, p.61-70 |
| issn | 0278-6915 1873-6351 |
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| source | ScienceDirect Journals |
| subjects | Absorption, Physiological Biomarkers - chemistry Biomarkers - metabolism Cell Line Cellular uptake Cytokines DNA Damage Glutathione - antagonists & inhibitors Glutathione - metabolism Humans Immunologic Factors - chemistry Immunologic Factors - toxicity Immunotoxicity Interleukin-1beta - agonists Interleukin-1beta - metabolism MAP Kinase Signaling System - drug effects Metal Nanoparticles - toxicity Metal Nanoparticles - ultrastructure Monocytes - drug effects Monocytes - immunology Monocytes - metabolism Monocytes - ultrastructure Mutagens - chemistry Mutagens - toxicity Nitric Oxide - agonists Nitric Oxide - metabolism Oxidative stress Oxidative Stress - drug effects Particle Size Reactive Oxygen Species - agonists Reactive Oxygen Species - metabolism Surface Properties Toxicity Tests Tumor Necrosis Factor-alpha - agonists Tumor Necrosis Factor-alpha - metabolism Zinc Oxide - chemistry Zinc Oxide - toxicity Zinc oxide nanoparticles |
| title | ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach |
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