title: Mechanisms of nanoparticle-induced oxidative stress and toxicity.
abstract: The rapidly emerging field of nanotechnology has offered innovative discoveries in the medical, industrial, and consumer sectors. The unique physicochemical and electrical properties of engineered nanoparticles (NP) make them highly desirable in a variety of applications. However, these novel properties of NP are fraught with concerns for environmental and occupational exposure. Changes in structural and physicochemical properties of NP can lead to changes in biological activities including ROS generation, one of the most frequently reported NP-associated toxicities. Oxidative stress induced by engineered NP is due to acellular factors such as particle surface, size, composition, and presence of metals, while cellular responses such as mitochondrial respiration, NP-cell interaction, and immune cell activation are responsible for ROS-mediated damage. NP-induced oxidative stress responses are torch bearers for further pathophysiological effects including genotoxicity, inflammation, and fibrosis as demonstrated by activation of associated cell signaling pathways. Since oxidative stress is a key determinant of NP-induced injury, it is necessary to characterize the ROS response resulting from NP. Through physicochemical characterization and understanding of the multiple signaling cascades activated by NP-induced ROS, a systemic toxicity screen with oxidative stress as a predictive model for NP-induced injury can be developed.
authors.affiliation: Department of Pharmaceutical Sciences and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Amruta
authors.initials: A
authors.lastname: Manke
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
mesh_terms: D004249:DNA Damage / Q000187:drug effects*; D004781:Environmental Exposure; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D016273:Occupational Exposure; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
references.citation: Exp Biol Med (Maywood). 2010 Sep;235(9):1025-33
references.pmid: 20719818
references.citation: J Nanosci Nanotechnol. 2010 May;10(5):3453-8
references.pmid: 20358977
references.citation: J Toxicol Environ Health A. 2003 Oct 24;66(20):1909-26
references.pmid: 14514433
references.citation: Nanotoxicology. 2011 Sep;5(3):312-25
references.pmid: 20925443
references.citation: Int J Nanomedicine. 2010 Nov 16;5:983-9
references.pmid: 21187917
references.citation: Environ Health Perspect. 2008 Sep;116(9):1211-7
references.pmid: 18795165
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L968-75
references.pmid: 11943661
references.citation: Free Radic Biol Med. 2008 May 1;44(9):1689-99
references.pmid: 18313407
references.citation: Crit Rev Toxicol. 2010 Apr;40(4):328-46
references.pmid: 20128631
references.citation: Toxicol In Vitro. 1998 Dec;12(6):649-59
references.pmid: 20654455
references.citation: Ethn Dis. 2010 Winter;20(1 Suppl 1):S1-65-72
references.pmid: 20521388
references.citation: Materials (Basel). 2010 Oct 25;3(10):4842-4859
references.pmid: 28883356
references.citation: Int J Nanomedicine. 2012;7:1203-14
references.pmid: 22419868
references.citation: Part Fibre Toxicol. 2005 Oct 06;2:8
references.pmid: 16209704
references.citation: J Environ Pathol Toxicol Oncol. 2001;20 Suppl 1:33-43
references.pmid: 11570672
references.citation: Toxicol Appl Pharmacol. 2006 Jul 1;214(1):16-23
references.pmid: 16410015
references.citation: J Biol Chem. 2003 Jun 6;278(23):20828-34
references.pmid: 12682076
references.citation: ACS Nano. 2010 Jun 22;4(6):3363-73
references.pmid: 20481555
references.citation: Environ Sci Technol. 2010 Nov 1;44(21):8337-42
references.pmid: 20932003
references.citation: Free Radic Biol Med. 2002 May 1;32(9):822-32
references.pmid: 11978484
references.citation: Chem Res Toxicol. 2012 Apr 16;25(4):828-37
references.pmid: 22263782
references.citation: Biomed Environ Sci. 2011 Dec;24(6):593-601
references.pmid: 22365394
references.citation: Occup Environ Med. 2004 Sep;61(9):727-8
references.pmid: 15317911
references.citation: J Toxicol Environ Health A. 2007 Dec;70(24):2071-9
references.pmid: 18049996
references.citation: ACS Nano. 2008 Jan;2(1):85-96
references.pmid: 19206551
references.citation: Inhal Toxicol. 2002 Jan;14(1):57-78
references.pmid: 12122560
references.citation: J Signal Transduct. 2011;2011:792639
references.pmid: 21637379
references.citation: Int J Nanomedicine. 2013;8:983-93
references.pmid: 23493450
references.citation: Toxicol In Vitro. 2012 Mar;26(2):351-61
references.pmid: 22210200
references.citation: Free Radic Biol Med. 2000 Feb 1;28(3):463-99
references.pmid: 10699758
references.citation: Regul Toxicol Pharmacol. 2011 Mar;59(2):251-7
references.pmid: 20955749
references.citation: J Toxicol Environ Health. 1993 Jul;39(3):341-54
references.pmid: 8394434
references.citation: J Toxicol Environ Health A. 2010;73(5):396-409
references.pmid: 20155581
references.citation: Biomaterials. 2010 Aug;31(23):5996-6003
references.pmid: 20466420
references.citation: Free Radic Res. 2008 Aug;42(8):437-745
references.pmid: 18712631
references.citation: Biochem Biophys Res Commun. 2010 May 28;396(2):578-83
references.pmid: 20447378
references.citation: Toxicol Appl Pharmacol. 2009 Jul 15;238(2):160-9
references.pmid: 19450615
references.citation: Biomaterials. 2007 Jul;28(19):2946-58
references.pmid: 17379299
references.citation: Toxicol In Vitro. 2009 Aug;23(5):808-15
references.pmid: 19401228
references.citation: Science. 2006 Feb 3;311(5761):622-7
references.pmid: 16456071
references.citation: IUBMB Life. 2001 Sep-Nov;52(3-5):159-64
references.pmid: 11798028
references.citation: J Biol Chem. 2005 Apr 15;280(15):14453-61
references.pmid: 15684422
references.citation: Chem Res Toxicol. 2011 Dec 19;24(12):2237-48
references.pmid: 22081859
references.citation: Environ Health Perspect. 1998 Oct;106 Suppl 5:1165-9
references.pmid: 9788892
references.citation: ACS Nano. 2009 Feb 24;3(2):279-90
references.pmid: 19236062
references.citation: Nanotoxicology. 2012 Feb;6(1):1-21
references.pmid: 21319953
references.citation: Food Chem Toxicol. 2012 Mar;50(3-4):641-7
references.pmid: 22273695
references.citation: Toxicol Appl Pharmacol. 2012 Jun 1;261(2):121-33
references.pmid: 22513272
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L1028-35
references.pmid: 16373669
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Nov;289(5):L698-708
references.pmid: 15951334
references.citation: J Am Chem Soc. 2003 Jul 2;125(26):7959-63
references.pmid: 12823017
references.citation: Gene. 2004 Aug 4;337:1-13
references.pmid: 15276197
references.citation: Redox Rep. 2003;8(3):143-50
references.pmid: 12935311
references.citation: Part Fibre Toxicol. 2012 Apr 10;9:10
references.pmid: 22490147
references.citation: IEEE Trans Nanobioscience. 2007 Dec;6(4):331-40
references.pmid: 18217626
references.citation: Toxicol Mech Methods. 2010 Jun;20(5):267-72
references.pmid: 20482408
references.citation: Chem Biol Interact. 2006 Mar 10;160(1):1-40
references.pmid: 16430879
references.citation: PLoS One. 2012;7(3):e30923
references.pmid: 22479306
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Mar;280(3):L442-9
references.pmid: 11159027
references.citation: Toxicol In Vitro. 2010 Feb;24(1):45-55
references.pmid: 19755143
references.citation: Biochem J. 1996 Jan 1;313 ( Pt 1):17-29
references.pmid: 8546679
references.citation: Clin Interv Aging. 2007;2(2):219-36
references.pmid: 18044138
references.citation: J Biol Chem. 2001 Mar 23;276(12):9108-14
references.pmid: 11096084
references.citation: Ann N Y Acad Sci. 1993 May 28;686:12-27; discussion 27-8
references.pmid: 8512242
references.citation: Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):42-59
references.pmid: 15650395
references.citation: Sci Total Environ. 2008 Aug 1;400(1-3):396-414
references.pmid: 18715626
references.citation: Biomed Environ Sci. 2011 Dec;24(6):661-9
references.pmid: 22365403
references.citation: Free Radic Biol Med. 2002 Dec 15;33(12):1622-40
references.pmid: 12488131
references.citation: Biointerphases. 2007 Dec;2(4):MR17-71
references.pmid: 20419892
references.citation: Toxicol Lett. 2010 Jun 16;196(1):21-7
references.pmid: 20362650
references.citation: Nano Lett. 2010 May 12;10(5):1677-81
references.pmid: 20369892
references.citation: Free Radic Biol Med. 2011 Nov 15;51(10):1872-81
references.pmid: 21920432
references.citation: Toxicol Appl Pharmacol. 1993 Jun;120(2):168-78
references.pmid: 8511786
references.citation: J Clin Toxicol. 2012;Suppl 5:
references.pmid: 26702365
references.citation: Part Fibre Toxicol. 2009 Jan 09;6:1
references.pmid: 19134195
references.citation: Environ Health Perspect. 2006 Sep;114(9):1325-30
references.pmid: 16966083
references.citation: J Toxicol Environ Health A. 2012;75(2):112-28
references.pmid: 22129238
references.citation: Toxicol Appl Pharmacol. 2006 Nov 15;217(1):7-14
references.pmid: 16930658
references.citation: ACS Nano. 2008 Oct 28;2(10):2121-34
references.pmid: 19206459
references.citation: Occup Environ Med. 2001 Mar;58(3):211-6, 199
references.pmid: 11171936
references.citation: Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2013;30(1):1-10
references.pmid: 23046173
references.citation: Free Radic Biol Med. 2003 Jun 15;34(12):1507-16
references.pmid: 12788471
references.citation: Nano Lett. 2006 Aug;6(8):1794-807
references.pmid: 16895376
references.citation: Nanotoxicology. 2013 Mar;7(2):157-68
references.pmid: 22263913
references.citation: Rev Environ Health. 2011;26(4):251-68
references.pmid: 22435324
references.citation: Toxicol Appl Pharmacol. 2002 Nov 1;184(3):172-9
references.pmid: 12460745
references.citation: Apoptosis. 2010 Dec;15(12):1507-16
references.pmid: 20694747
references.citation: J Environ Sci Health A Tox Hazard Subst Environ Eng. 2006;41(12):2699-711
references.pmid: 17114101
references.citation: Eur J Pharm Biopharm. 2012 Jun;81(2):324-33
references.pmid: 22446064
references.citation: Toxicol In Vitro. 2009 Oct;23(7):1365-71
references.pmid: 19699289
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Oct;295(4):L552-65
references.pmid: 18658273
references.citation: Toxicol In Vitro. 2010 Apr;24(3):751-8
references.pmid: 20060462
references.citation: Toxicol Appl Pharmacol. 2012 Mar 15;259(3):281-92
references.pmid: 22280989
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L488-96
references.pmid: 15557088
references.citation: Part Fibre Toxicol. 2006 Aug 14;3:11
references.pmid: 16907977
references.citation: J Toxicol Environ Health A. 2004 Jan 9;67(1):87-107
references.pmid: 14668113
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 May;284(5):L774-82
references.pmid: 12676768
references.citation: Res Rep Health Eff Inst. 2009 Jan;(136):3-32
references.pmid: 19552347
references.citation: Mutat Res. 2005 Dec 30;592(1-2):119-37
references.pmid: 16085126
references.citation: Toxicol Sci. 2007 Nov;100(1):203-14
references.pmid: 17660506
references.citation: Mcgill J Med. 2008 Jan;11(1):43-50
references.pmid: 18523535
references.citation: J Nanosci Nanotechnol. 2007 Jul;7(7):2466-72
references.pmid: 17663266
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Sep;283(3):L528-30
references.pmid: 12169571
references.citation: Toxicol Sci. 2003 Sep;75(1):181-91
references.pmid: 12832661
references.citation: Mutat Res. 2011 Apr 3;721(2):184-91
references.pmid: 21296185
references.citation: Part Fibre Toxicol. 2009 Jun 12;6:16
references.pmid: 19523217
references.citation: Immunobiology. 2009;214(2):121-8
references.pmid: 19167990
references.citation: Toxicol Sci. 2004 Jan;77(1):117-25
references.pmid: 14514968
references.citation: Analyst. 2011 Apr 7;136(7):1279-87
references.pmid: 21311804
references.citation: Toxicol Lett. 2008 Jul 10;179(3):130-9
references.pmid: 18547751
references.citation: Inhal Toxicol. 2002 Jan;14(1):5-27
references.pmid: 12122558
references.citation: Toxicology. 2008 Mar 12;245(1-2):90-100
references.pmid: 18243471
references.citation: J Clin Biochem Nutr. 2012 May;50(3):211-6
references.pmid: 22573923
references.citation: Environ Health Perspect. 1997 Sep;105 Suppl 5:1073-84
references.pmid: 9400703
references.citation: Free Radic Biol Med. 2007 Jan 15;42(2):191-201
references.pmid: 17189825
references.citation: Int J Nanomedicine. 2013;8:1129-40
references.pmid: 23515466
references.citation: Am Rev Respir Dis. 1993 Jan;147(1):134-8
references.pmid: 8420406
references.citation: Swiss Med Wkly. 2012 Nov 05;142:w13698
references.pmid: 23444280
references.citation: Carcinogenesis. 1995 Oct;16(10):2401-5
references.pmid: 7586142
references.citation: Nanomedicine. 2011 Dec;7(6):904-13
references.pmid: 21664489
references.citation: Toxicol Appl Pharmacol. 2011 Aug 15;255(1):18-31
references.pmid: 21624382
references.citation: Histol Histopathol. 2013 Feb;28(2):195-209
references.pmid: 23275303
references.citation: Toxicol Appl Pharmacol. 2011 Apr 1;252(1):1-10
references.pmid: 21310169
references.citation: Toxicol In Vitro. 2013 Feb;27(1):330-8
references.pmid: 22940466
references.citation: Carcinogenesis. 2008 Feb;29(2):427-33
references.pmid: 18174261
references.citation: Science. 2005 May 6;308(5723):804-6
references.pmid: 15879201
references.citation: Toxicol In Vitro. 2013 Mar;27(2):731-8
references.pmid: 23232460
references.citation: Biomaterials. 2013 May;34(14):3559-70
references.pmid: 23433773
references.citation: J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Apr;27(2):120-39
references.pmid: 19412858
references.citation: Environ Health Perspect. 2005 Aug;113(8):947-55
references.pmid: 16079062
references.citation: Adv Exp Med Biol. 2001;500:489-96
references.pmid: 11764986
references.citation: Environ Sci Technol. 2009 Jun 15;43(12):4555-60
references.pmid: 19603676
references.citation: Int Arch Occup Environ Health. 2006 Oct;80(1):1-15
references.pmid: 16685565
references.citation: Toxicology. 2009 Jun 16;260(1-3):37-46
references.pmid: 19464567
references.citation: Toxicol Sci. 2009 Feb;107(2):342-51
references.pmid: 19023088
references.citation: Toxicology. 2011 May 10;283(2-3):101-8
references.pmid: 21382431
references.citation: Environ Toxicol Pharmacol. 2010 Mar;29(2):131-7
references.pmid: 21787594
references.citation: J Physiol. 2003 Oct 15;552(Pt 2):335-44
references.pmid: 14561818
references.citation: Part Fibre Toxicol. 2010 Mar 22;7:5
references.pmid: 20307263
references.citation: J Am Soc Nephrol. 2004 Feb;15(2):370-9
references.pmid: 14747383
references.citation: Toxicology. 2009 Mar 29;257(3):161-71
references.pmid: 19150385
references.citation: Crit Rev Toxicol. 2003;33(1):61-103
references.pmid: 12585507
references.citation: J Biol Chem. 1996 Feb 23;271(8):4138-42
references.pmid: 8626753
references.citation: J Toxicol Environ Health A. 2010;73(5):410-22
references.pmid: 20155582
references.citation: Toxicol Sci. 2002 Jun;67(2):275-83
references.pmid: 12011487
references.citation: Toxicol In Vitro. 2011 Feb;25(1):231-41
references.pmid: 21092754
references.citation: Toxicol Lett. 2009 Jul 24;188(2):112-8
references.pmid: 19446243
references.citation: Toxicol Pathol. 2007 Jan;35(1):148-53
references.pmid: 17325983
references.citation: Cell Biochem Biophys. 2013 Nov;67(2):461-76
references.pmid: 22669739
references.citation: Int J Cancer. 2004 May 10;109(6):799-809
references.pmid: 15027112
references.citation: Cell Signal. 2007 Sep;19(9):1807-19
references.pmid: 17570640
references.citation: Exp Biol Med (Maywood). 2008 Feb;233(2):109-22
references.pmid: 18222966
references.citation: Carcinogenesis. 1996 Mar;17(3):413-9
references.pmid: 8631125
references.citation: Environ Toxicol. 2010 Dec;25(6):608-21
references.pmid: 20549644
references.citation: Int J Toxicol. 2006 Nov-Dec;25(6):451-7
references.pmid: 17132603
references.citation: Eur J Biochem. 1997 Mar 1;244(2):587-95
references.pmid: 9119028
references.citation: Apoptosis. 2012 Aug;17(8):852-70
references.pmid: 22395444
references.citation: Environ Health Perspect. 1997 Feb;105 Suppl 1:165-77
references.pmid: 9114285
references.citation: Part Fibre Toxicol. 2010 Aug 21;7:22
references.pmid: 20727197
references.citation: Toxicol Appl Pharmacol. 2008 Oct 15;232(2):292-301
references.pmid: 18706438
references.citation: Toxicol Lett. 2007 Jan 10;168(1):58-74
references.pmid: 17141434
references.citation: Biointerphases. 2011 Jun;6(2):P1-17
references.pmid: 21721837
references.citation: J Biol Chem. 2009 Jan 9;284(2):717-21
references.pmid: 18757361
references.citation: Toxicol Appl Pharmacol. 2010 Aug 1;246(3):116-27
references.pmid: 20434478
references.citation: Toxicol Sci. 2004 Jan;77(1):126-34
references.pmid: 14514958
references.citation: Toxicol Lett. 2009 Jun 1;187(2):77-83
references.pmid: 19429248
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1005-28
references.pmid: 11076791
references.citation: Part Fibre Toxicol. 2011 Mar 03;8:10
references.pmid: 21371295
references.citation: Nano Lett. 2005 Sep;5(9):1676-84
references.pmid: 16159204
references.citation: Free Radic Biol Med. 2004 Sep 1;37(5):582-93
references.pmid: 15288116
references.citation: Swiss Med Wkly. 2012 Jun 19;142:w13547
references.pmid: 22714122