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Review

The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes

, , , &
Pages 8787-8804 | Published online: 07 Nov 2019

References

  • Khan I, Saeed K, Khan I. Nanoparticles: properties, applications and toxicities. Arab J Chem. 2017;21(3):541–548.
  • Parada J, Rubilar O, Fernández-Baldo MA, et al. The nanotechnology among US: are metal and metal oxides nanoparticles a nano or mega risk for soil microbial communities? Crit Rev Biotechnol. 2018;39(2):157–172. doi:10.1080/07388551.2018.152386530396282
  • Andra S, Balu SK, Jeevanandham J. Phytosynthesized metal oxide nanoparticles for pharmaceutical applications. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(7):755–771. doi:10.1007/s00210-019-01666-731098696
  • Amde M, Liu JF, Tan ZQ, Bekana D. Transformation and bioavailability of metal oxide nanoparticles in aquatic and terrestrial environments. A review. Environ Pollut. 2017;230:250–267. doi:10.1016/j.envpol.2017.06.06428662490
  • Yah CS, Iyuke SE, Simate GS. A review of nanoparticles toxicity and their routes of exposures. Iran J Pharm Res. 2012;8(1):299–314.
  • Gustafson HH, Holt-Casper D, Grainger DW, Ghandehari H. Nanoparticle uptake: the phagocyte problem. Nano Today. 2015;10(4):487–510. doi:10.1016/j.nantod.2015.06.00626640510
  • Almeida JPM, Chen AL, Foster A, Drezek R. In vivo biodistribution of nanoparticles. Nanomedicine. 2011;6(5):815–835. doi:10.2217/nnm.11.7921793674
  • Li TZ, Gong F, Zhang BY, et al. [Acute toxicity and bio-distribution of silver nitrate and nano-silver with different particle diameters in rats]. Chin J Burns. 2016;32(10):606–612. doi:10.3760/cma.j.issn.1009-2587.2016.10.007
  • Kreyling WG, Möller W, Holzwarth U, et al. Age-dependent rat lung deposition patterns of inhaled 20 nanometer gold nanoparticles and their quantitative biokinetics in adult rats. ACS Nano. 2018;12(8):7771–7790. doi:10.1021/acsnano.8b0182630085651
  • Chinde S, Grover P. Toxicological assessment of nano and micron-sized tungsten oxide after 28days repeated oral administration to Wistar rats. Mutat Res. 2017;819:1–13. doi:10.1016/j.mrgentox.2017.05.00328622824
  • Liu F, Chang X, Tian M, et al. Nano NiO induced liver toxicity via activating the NF-κB signaling pathway in rats. Toxicol Res (Camb). 2017;6(2):242–250. doi:10.1039/C6TX00444J30090495
  • Tang H, Min X, Fei S, et al. Effects and mechanism of nano-copper exposure on hepatic cytochrome P450 enzymes in rats. Int J Mol Sci. 2018;19(7):2140. doi:10.3390/ijms19072140
  • Jia J, Li F, Zhou H, et al. Oral exposure of silver nanoparticles or silver ions may aggravate fatty liver disease in overweight mice. Environ Sci Technol. 2017;51(16):9334–9343. doi:10.1021/acs.est.7b0275228723108
  • Azim SAA, Darwish HA, Rizk MZ, Ali SA, Mai OK. Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: possible role of some antioxidants. Exp Toxicol Pathol. 2015;67(4):305–314. doi:10.1016/j.etp.2015.02.00125739888
  • Sha B, Gao W, Wang S, et al. Oxidative stress increased hepatotoxicity induced by nano-titanium dioxide in BRL-3A cells and Sprague-Dawley rats. J Appl Toxicol. 2014;34(4):345–356. doi:10.1002/jat.290023873220
  • Magaye RR, Yue X, Zou B, et al. Acute toxicity of nickel nanoparticles in rats after intravenous injection. Int J Nanomedicine. 2014;2014(1):1393–1402.
  • Recordati C, De Maglie M, Bianchessi S, et al. Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects. Part Fibre Toxicol. 2016;13:12. doi:10.1186/s12989-016-0124-x26926244
  • Suker DK, Jasim FA. Liver histopathological alteration after repeated intra-tracheal instillation of titanium dioxide in male rats. Gastroenterol Hepatol Bed Bench. 2018;11(2):159–168.29910858
  • Matthias B, Thomas R, Keul HA, et al. Peptide-functionalized gold nanorods increase liver injury in hepatitis. ACS Nano. 2012;6(10):8767–8777. doi:10.1021/nn302502u22994679
  • Wang C, Cheng K, Zhou L, et al. Evaluation of long-term toxicity of oral zinc oxide nanoparticles and zinc sulfate in mice. Biol Trace Elem Res. 2017;178(2):276–282. doi:10.1007/s12011-017-0934-128120304
  • Yu S, Liu F, Wang C, et al. Role of oxidative stress in liver toxicity induced by nickel oxide nanoparticles in rats. Mol Med Rep. 2018;17(2):3133–3139. doi:10.3892/mmr.2017.822629257258
  • Mei-Lang K, Shu-Ling H, Chih-Chung W, et al. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells. Nanoscale. 2015;7(5):1820–1829. doi:10.1039/C4NR05843G25521936
  • Ali D, Alarifi S, Alkahtani S, Almeer RS. Silver-doped graphene oxide nanocomposite triggers cytotoxicity and apoptosis in human hepatic normal and carcinoma cells. Int J Nanomedicine. 2018;13:5685–5699. doi:10.2147/IJN30288041
  • Vrček IV, Žuntar I, Petlevski R, et al. Comparison of in vitro toxicity of silver ions and silver nanoparticles on human hepatoma cells. Environ Toxicol. 2016;31(6):679–692. doi:10.1002/tox.v31.625448069
  • Grzelak A, Wojewodzka M, Meczynska-Wielgosz S, Zuberek M, Wojciechowska D, Kruszewski M. Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity. Redox Biol. 2018;15:435–440. doi:10.1016/j.redox.2018.01.00629351884
  • Mishra AR, Zheng J, Tang X, Goering PL. Silver nanoparticle-induced autophagic-lysosomal disruption and NLRP3-inflammasome activation in HepG2 cells is size-dependent. Toxicol Sci. 2016;150(2):473–487. doi:10.1093/toxsci/kfw01126801583
  • Piao MJ, Kang KA, Lee IK, et al. Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. Toxicol Lett. 2011;201(1):92–100. doi:10.1016/j.toxlet.2010.12.01021182908
  • Wang T, Chen X, Long X, Liu Z, Copper Nanoparticles YS. Copper sulphate induced cytotoxicity in hepatocyte primary cultures of epinephelus coioides. PLoS One. 2016;11(2):e0149484. doi:10.1371/journal.pone.014948426890000
  • Wang Y, Aker WG, Hwang HM, Yedjou CG, Yu H, Tchounwou PB. A study of the mechanism of in vitro cytotoxicity of metal oxide nanoparticles using catfish primary hepatocytes and human HepG2 cells. Sci Total Environ. 2011;409(22):4753–4762. doi:10.1016/j.scitotenv.2011.07.03921851965
  • Natarajan V, Wilson CL, Hayward SL, Kidambi S. Titanium dioxide nanoparticles trigger loss of function and perturbation of mitochondrial dynamics in primary hepatocytes. PLoS One. 2015;10(8):e0134541. doi:10.1371/journal.pone.013454126247363
  • Saquib Q, Siddiqui MA, Ahmad J, et al. Nickel oxide nanoparticles induced transcriptomic alterations in HEPG2 cells. Exp Biol Med. 2018;1048(10):163–174.
  • Sun X, Wang Z, Zhai S, Cheng Y, Liu J, Liu B. In vitro cytotoxicity of silver nanoparticles in primary rat hepatic stellate cells. Mol Med Rep. 2013;8(5):1365–1372. doi:10.3892/mmr.2013.168324043207
  • Liu S, Shen Z, Wu B, et al. Cytotoxicity and efflux pump inhibition induced by molybdenum disulfide and boron nitride nanomaterials with sheetlike structure. Environ Sci Technol. 2017;51(18):10834–10842. doi:10.1021/acs.est.7b0246328841301
  • Chen R, Zhao L, Bai R, et al. Silver nanoparticles induced oxidative and endoplasmic reticulum stresses in mouse tissues: implications for the development of acute toxicity after intravenous administration. Toxicol Res (Camb). 2016;5(2):602–608. doi:10.1039/C5TX00464K30090374
  • Almansour M, Sajti L, Melhim W, Jarrar B. Ultrastructural hepatic alterations induced by 35 nm zinc oxide nanoparticles. Nanosci. 2015;7(9):763–769. doi:10.1166/nnl.2015.2028
  • Yang J, Luo M, Tan Z, et al. Oral administration of nano-titanium dioxide particle disrupts hepatic metabolic functions in a mouse model. Environ Toxicol Pharmacol. 2017;49:112–118. doi:10.1016/j.etap.2016.12.00627984778
  • Jana P, Bojana Z, Magdalena S, et al. DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology. 2011;5(3):341–353. doi:10.3109/17435390.2010.50731621067279
  • Mirshafiee V, Sun B, Chang CH, et al. Toxicological profiling of metal oxide nanoparticles in liver context reveals pyroptosis in kupffer cells and macrophages versus apoptosis in hepatocytes. ACS Nano. 2018;12(4):3836–3852. doi:10.1021/acsnano.8b0108629543433
  • Paesano L, Perotti A, Buschini A, et al. Markers for toxicity to HepG2 exposed to cadmium sulphide quantum dots; damage to mitochondria. Toxicology. 2016;374(2016):18–28. doi:10.1016/j.tox.2016.11.01227866839
  • Nguyen KC, Rippstein P, Tayabali AF, Willmore WG. Mitochondrial toxicity of cadmium telluride quantum dot nanoparticles in mammalian hepatocytes. Toxicol Sci. 2015;146(1):31–42. doi:10.1093/toxsci/kfv06825809595
  • Maurer LL, Meyer JN. A systematic review of evidence for silver nanoparticle-induced mitochondrial toxicity. Environ Sci Nano. 2016;3(2):311–322.
  • Kuang H, Yang P, Yang L, Aguilar ZP, Xu H. Size dependent effect of ZnO nanoparticles on endoplasmic reticulum stress signaling pathway in murine liver. J Hazard Mater. 2016;317:119–126. doi:10.1016/j.jhazmat.2016.05.06327262279
  • Yu KN, Sung JH, Lee S, et al. Inhalation of titanium dioxide induces endoplasmic reticulum stress-mediated autophagy and inflammation in mice. Food Chem Toxicol. 2015;85:106–113. doi:10.1016/j.fct.2015.08.00126253354
  • Yang X, Shao H, Liu W, et al. Endoplasmic reticulum stress and oxidative stress are involved in ZnO nanoparticle-induced hepatotoxicity. Toxicol Lett. 2015;234(1):40–49. doi:10.1016/j.toxlet.2015.02.00425680694
  • He C, Jiang S, Yao H, et al. Endoplasmic reticulum stress mediates inflammatory response triggered by ultra-small superparamagnetic iron oxide nanoparticles in hepatocytes. Nanotoxicology. 2018;12(10):1198–1214. doi:10.1080/17435390.2018.153038830422028
  • Condello M, De Berardis B, Ammendolia MG, et al. ZnO nanoparticle tracking from uptake to genotoxic damage in human colon carcinoma cells. Toxicol In Vitro. 2016;35:169–179. doi:10.1016/j.tiv.2016.06.00527317967
  • Sarhan OM, Hussein RM. Effects of intraperitoneally injected silver nanoparticles on histological structures and blood parameters in the albino rat. Int J Nanomedicine. 2014;9:1505–1517. doi:10.2147/IJN.S5672924711700
  • Wang J, Yu Y, Lu K, et al. Silica nanoparticles induce autophagy dysfunction via lysosomal impairment and inhibition of autophagosome degradation in hepatocytes. Int J Nanomedicine. 2017;12:809–825. doi:10.2147/IJN.S12359628182147
  • Gatoo MA, Naseem S, Arfat MY, Mahmood Dar A, Qasim K, Zubair S. Physicochemical properties of nanomaterials: implication in associated toxic manifestations. Biomed Res Int. 2014;2014:498420. doi:10.1155/2014/49842025165707
  • Lopez-Chaves C, Soto-Alvaredo J, Montes-Bayon M, Bettmer J, Llopis J, Sanchez-Gonzalez C. Gold nanoparticles: distribution, bioaccumulation and toxicity. In vitro and in vivo studies. Nanomed. 2018;14(1):1–12. doi:10.1016/j.nano.2017.08.011
  • Gao B, Xu J, He KW, et al. Cellular uptake and intra-organ biodistribution of functionalized silica-coated gold nanorods. Mol Imaging Biol. 2016;18(5):667–676. doi:10.1007/s11307-016-0938-926884056
  • Peng F, Su Y, Zhong Y, He Y. Subcellular distribution and cellular self-repair ability of fluorescent quantum dots emitting in the visible to near-infrared region. Nanotechnology. 2017;28(4):045101. doi:10.1088/1361-6528/28/4/04510127977421
  • Xie X, Liao J, Shao X, Li Q, Lin Y. The effect of shape on cellular uptake of gold nanoparticles in the forms of stars, rods, and triangles. Sci Rep. 2017;7(1):3827. doi:10.1038/s41598-017-04229-z28630477
  • Almansour MI, Alferah MA, Shraideh ZA, Jarrar BM. Zinc oxide nanoparticles hepatotoxicity: histological and histochemical study. Environ Toxicol Pharmacol. 2017;51:124–130. doi:10.1016/j.etap.2017.02.01528236584
  • Tsoi KM, MacParland SA, Ma XZ, et al. Mechanism of hard-nanomaterial clearance by the liver. Nat Mater. 2016;15(11):1212–1221. doi:10.1038/nmat471827525571
  • Sykes EA, Chen J, Zheng G, Chan WC. Investigating the impact of nanoparticle size on active and passive tumor targeting efficiency. ACS Nano. 2014;8(6):5696–5706. doi:10.1021/nn500299p24821383
  • Perrault SD, Walkey C, Jennings T, Fischer HC, Chan WC. Mediating tumor targeting efficiency of nanoparticles through design. Nano Lett. 2009;9(5):1909–1915. doi:10.1021/nl900031y19344179
  • Suganthy N, Sri Ramkumar V, Pugazhendhi A, Benelli G, Archunan G. Biogenic synthesis of gold nanoparticles from terminalia arjuna bark extract: assessment of safety aspects and neuroprotective potential via antioxidant, anticholinesterase, and antiamyloidogenic effects. Environ Sci Pollut Res. 2018;25(11):10418–10433. doi:10.1007/s11356-017-9789-4
  • Pugazhendhi A, Tnji E, Karuppusamy I, Kathirvel B. Inorganic nanoparticles: a potential cancer therapy for human welfare. Int J Pharm. 2018;539(1–2):104–111. doi:10.1016/j.ijpharm.2018.01.03429366941
  • Pilapong C, Sitthichai S, Thongtem S, Thongtem T. Smart magnetic nanoparticle-aptamer probe for targeted imaging and treatment of hepatocellular carcinoma. Int J Pharm. 2014;473(1–2):469–474. doi:10.1016/j.ijpharm.2014.07.03625089503
  • England CG, Priest T, Zhang G, et al. Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles. Int J Nanomedicine. 2013;8:3603–3617. doi:10.2147/IJN.S5166824124360
  • Jiang Z, Shan K, Song J, et al. Toxic effects of magnetic nanoparticles on normal cells and organs. Life Sci. 2019;220:156–161. doi:10.1016/j.lfs.2019.01.05630716338
  • Krishnan SK, Kumar PSM. Controlled synthesis of Pt nanoparticle supported TiO2 nanorods as efficient and stable electrocatalyst for oxygen reduction reaction. J Mater Chem. 2018;6:46.
  • Murphin Kumar PS, Thiripuranthagan S, Imai T, et al. Pt nanoparticles supported on mesoporous CeO2 nanostructures obtained through green approach for efficient catalytic performance towards ethanol electrooxidation. ACS Sustain Chem Eng. 2017;5:12. doi:10.1021/acssuschemeng.7b02019
  • Han X, Gelein R, Corson N, et al. Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology. 2011;287(1):99–104. doi:10.1016/j.tox.2011.06.01121722700
  • Lee IC, Ko JW, Park SH, et al. Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats. Int J Nanomedicine. 2016;11:2883–2900. doi:10.2147/IJN.S10634627366066
  • Falfushynska H, Gnatyshyna L, Horyn O, Shulgai A, Stoliar O. A calcium channel blocker nifedipine distorts the effects of nano-zinc oxide on metal metabolism in the marsh frog Pelophylax ridibundus. Saudi J Biol Sci. 2019;26(3):481–489. doi:10.1016/j.sjbs.2017.10.00430899162
  • Wenhong F, Qian L, Xiuping Y, Li Z. Zn subcellular distribution in liver of goldfish (carassius auratus) with exposure to zinc oxide nanoparticles and mechanism of hepatic detoxification. PLoS One. 2013;8(11):e78123. doi:10.1371/journal.pone.007812324223767
  • Rang FJ, Boonstra J. Causes and consequences of age-related changes in DNA methylation: a role for ROS? Biology. 2014;3(2):403–425. doi:10.3390/biology302040324945102
  • Cichożlach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014;20(25):8082–8091. doi:10.3748/wjg.v20.i25.808225009380
  • Liu H, Ma L, Liu J, Zhao J, Yan J, Hong F. Toxicity of nano-anatase TiOto mice: liver injury, oxidative stress. Environ Toxicol Chem. 2010;92(1):175–186.
  • Pereira LC, Pazin M, Franco-Bernardes MF, et al. A perspective of mitochondrial dysfunction in rats treated with silver and titanium nanoparticles (AgNPs and TiNPs). J Trace Elem Med Biol. 2018;47:63–69. doi:10.1016/j.jtemb.2018.01.00729544809
  • Blanco J, Tomas-Hernandez S, Garcia T, et al. Oral exposure to silver nanoparticles increases oxidative stress markers in the liver of male rats and deregulates the insulin signalling pathway and p53 and cleaved caspase 3 protein expression. Food Chem Toxicol. 2018;115:398–404. doi:10.1016/j.fct.2018.03.03929604305
  • Reddy UA, Prabhakar PV, Mahboob M. Comparative study of nano and bulk Fe3O4 induced oxidative stress in Wistar rats. Biomarkers. 2018;23(5):425–434. doi:10.1080/1354750X.2018.144350829458263
  • Jia X, Wang S, Zhou L, Sun L. The potential liver, brain, and embryo toxicity of titanium dioxide nanoparticles on mice. Nanoscale Res Lett. 2017;12(1):478. doi:10.1186/s11671-017-2242-228774157
  • Gokduman K, Bestepe F, Li L, Yarmush ML, Usta OB. Dose-, treatment- and time-dependent toxicity of superparamagnetic iron oxide nanoparticles on primary rat hepatocytes. Nanomedicine. 2018;13(11):1267–1284. doi:10.2217/nnm-2017-038729949471
  • Degli Esposti D, Hamelin J, Bosselut N, et al. Mitochondrial roles and cytoprotection in chronic liver injury. Biochem Res Int. 2012;387626.22745910
  • Thai SF, Wallace KA, Jones CP, et al. Differential genomic effects of six different TiO2 nanomaterials on human liver HepG2 cells. J Biochem Mol Toxicol. 2016;30(7):331–341. doi:10.1002/jbt.2179826918567
  • Liu H-L, Yang H-L, Lin B-C, et al. Toxic effect comparison of three typical sterilization nanoparticles on oxidative stress and immune inflammation response in rats. Toxicol Res (Camb). 2015;4(2):486–493. doi:10.1039/C4TX00154K
  • Gaiser BK, Hirn S, Kermanizadeh A, et al. Effects of silver nanoparticles on the liver and hepatocytes in vitro. Toxicol Sci. 2013;131(2):537–547. doi:10.1093/toxsci/kfs30623086748
  • Prasenjit M, Manoranjan G, Jyotirmoy G, Joydeep D, Sil PC. Contribution of nano-copper particles to in vivo liver dysfunction and cellular damage: role of IκBα/NF-κB, MAPKs and mitochondrial signal. Nanotoxicology. 2012;6(1):1–21. doi:10.3109/17435390.2011.55212421319953
  • Zhu B, Li Y, Lin Z, et al. Silver nanoparticles induce HePG-2 cells apoptosis through ROS-mediated signaling pathways. Nanoscale Res Lett. 2016;11(1):198. doi:10.1186/s11671-016-1419-427075340
  • Kerr JFR, Wyllie AH, Currie AR. Apoptosis_A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239–257. doi:10.1038/bjc.1972.334561027
  • Zhou WC, Zhang QB, Liang Q. Pathogenesis of liver cirrhosis. Med Klin. 2014;20(23):278–280.
  • Kanda T, Matsuoka S, Yamazaki M, et al. Apoptosis and non-alcoholic fatty liver diseases. World J Gastroenterol. 2018;24(25):2661–2672. doi:10.3748/wjg.v24.i25.266129991872
  • Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol. 2013;3(2):977–1010. doi:10.1002/cphy.c12002023720337
  • Chen YY, Ou YS, Tao Y, et al. Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells. Oncol Rep. 2018;40(4):2260–2268. doi:10.3892/or.2018.661930106429
  • Savitskaya MA, Onishchenko GE. Mechanisms of apoptosis. Biochem.-Moscow. 2015;80(11):1393–1405. doi:10.1134/S0006297915110012
  • Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008;9(3):231–241. doi:10.1038/nrm231218073771
  • Günther C, Neumann H, Neurath MF, Becker C. Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut. 2013;62(7):1062–1071. doi:10.1136/gutjnl-2011-30136422689519
  • Adrain C, SJ M. The mitochondrial apoptosome_a killer unleashed by the cytochrome seas. Trends Biochem Sci. 2001;26(6):390–397. doi:10.1016/S0968-0004(01)01844-811406413
  • Arnoult D, Gaume B, Karbowski M, Sharpe JC, Cecconi F, Youle RJ. Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax_Bak-mediated permeabilization. Embo J. 2003;22(17):4385–4399. doi:10.1093/emboj/cdg42312941691
  • Kitagawa N, Morikawa T, Motai C, et al. The antiproliferative effect of chakasaponins I and II, floratheasaponin A, and epigallocatechin 3-O-gallate isolated from camellia sinensis on human digestive tract carcinoma cell lines. Int J Mol Sci. 2016;17(12):1–16. doi:10.3390/ijms17121979
  • Morgan A, Ibrahim MA, Galal MK, Ogaly HA, Abd-Elsalam RM. Innovative perception on using Tiron to modulate the hepatotoxicity induced by titanium dioxide nanoparticles in male rats. Biomed Pharmacother. 2018;103:553–561. doi:10.1016/j.biopha.2018.04.06429677542
  • El-Sherbiny IM, Salih E, Yassin AM, Hafez EE. Newly developed chitosan-silver hybrid nanoparticles: biosafety and apoptosis induction in HepG2 cells. J Nanopart Res. 2016;18(7):172. doi:10.1007/s11051-016-3477-z
  • Su H, Li Z, Lazar L, et al. In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus Fe3O4 -TiO2 nanoparticles in human liver cells. Environ Toxicol. 2018;33(10):1078–1088. doi:10.1002/tox.2263130098274
  • Xue Y, Wang J, Huang Y, et al. Comparative cytotoxicity and apoptotic pathways induced by nanosilver in human liver HepG2 and L02 cells. Hum Exp Toxicol. 2018;37(12):1293–1309. doi:10.1177/096032711876971829658330
  • Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221(1):3–12. doi:10.1002/path.269720225336
  • Karen P, Manshian BB, Freya J, et al. Exploiting intrinsic nanoparticle toxicity: the pros and cons of nanoparticle-induced autophagy in biomedical research. Chem Rev. 2014;114(15):7581. doi:10.1021/cr400372p24927160
  • Ueno T, Komatsu M. Autophagy in the liver: functions in health and disease. Nat Rev Gastroenterol Hepatol. 2017;14(3):170–184. doi:10.1038/nrgastro.2016.18528053338
  • Wan J, Wang JH, Liu T, Xie Z, Yu XF, Li W. Surface chemistry but not aspect ratio mediates the biological toxicity of gold nanorods in vitro and in vivo. Sci Rep. 2015;5:11398. doi:10.1038/srep1139826096816
  • Zhu S, Zhang J, Zhang L, et al. Inhibition of kupffer cell autophagy abrogates nanoparticle-induced liver injury. Adv Healthc Mater. 2017;6(9):1–11. doi:10.1002/adhm.201601252
  • Saowalak K, Titipun T, Somchai T, Chalermchai P. Iron(III)-tannic molecular nanoparticles enhance autophagy effect and T1MRI contrast in liver cell lines. Sci Rep. 2018;8(1):6647. doi:10.1038/s41598-018-25108-129703912
  • Kermanizadeh A, Jantzen K, Ward MB, et al. Nanomaterial-induced cell death in pulmonary and hepatic cells following exposure to three different metallic materials: the role of autophagy and apoptosis. Nanotoxicology. 2017;11(2):184–200. doi:10.1080/17435390.017.127935928055265
  • Lim Y, Kumar S. A single cut to pyroptosis. Oncotarget. 2015;6(35):36926–36927. doi:10.18632/oncotarget.v6i3526485769
  • Lei-Leston AC, Murphy AG, Maloy KJ. Epithelial cell inflammasomes in intestinal immunity and inflammation. Front Immunol. 2017;8:1168. doi:10.3389/fimmu.2017.0116828979266
  • Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660–665. doi:10.1038/nature1551426375003
  • Byrne BG, Dubuisson JF, Joshi AD, Persson JJ, Swanson MS. Inflammasome components coordinate autophagy and pyroptosis as macrophage responses to infection. Am Soc Microbiol. 2013;4(1):e00620–e00612.
  • Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7(2):99–109. doi:10.1038/nrmicro207019148178
  • Fink SL, Cookson BT. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol. 2006;8(11):1812–1825. doi:10.1111/cmi.2006.8.issue-1116824040
  • Guo H, Xie M, Zhou C, Zheng M. The relevance of pyroptosis in the pathogenesis of liver diseases. Life Sci. 2019;223:69–73. doi:10.1016/j.lfs.2019.02.06030831126
  • Man SM, Karki R, Kanneganti T-D. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 2017;277(1):61–75. doi:10.1111/imr.2017.277.issue-128462526
  • Kofahi HM, Taylor NGA, Hirasawa K, Grant MD, Russell RS. Hepatitis C virus infection of cultured human hepatoma cells causes apoptosis and pyroptosis in both infected and bystander cells. Sci Rep. 2016;6:37433. doi:10.1038/srep3743327974850
  • Dumkova J, Smutna T, Vrlikova L, et al. Sub-chronic inhalation of lead oxide nanoparticles revealed their broad distribution and tissue-specific subcellular localization in target organs. Part Fibre Toxicol. 2017;14(1):55. doi:10.1186/s12989-017-0236-y29268755
  • Xiao M, Chen W, Wang C, et al. Senescence and cell death in chronic liver injury: roles and mechanisms underlying hepatocarcinogenesis. Oncotarget. 2017;9(9):8772–8784. doi:10.18632/oncotarget.2362229492237
  • Wu M-Y, Yiang G-T, Cheng P-W, Chu P-Y, Li C-J. Molecular targets in hepatocarcinogenesis and implications for therapy. J Clin Med. 2018;7(8):213. doi:10.3390/jcm7080213