Skip to main content
Log in

Magnetite induces oxidative stress and apoptosis in lung epithelial cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

An Erratum to this article was published on 08 March 2013

Abstract

There is an ongoing concern regarding the biocompatibility of nanoparticles with sizes less than 100 nm as compared to larger particles of the same nominal substance. In this study, we investigated the toxic properties of magnetite stabilized with polyacrylate sodium. The magnetite was characterized by X-ray powder diffraction analysis, and the mean particle diameter was calculated using the Scherrer formula and was found to be 9.3 nm. In this study, we treated lung epithelial cells with different concentrations of magnetite and investigated their effects on oxidative stress and cell proliferation. Our data showed an inhibition of cell proliferation in magnetite-treated cells with a significant dose-dependent activation and induction of reactive oxygen species. Also, we observed a depletion of antioxidants, glutathione, and superoxide dismutase, respectively, as compared with control cells. In addition, apoptotic-related protease/enzyme such as caspase-3 and -8 activities, were increased in a dose-dependent manner with corresponding increased levels of DNA fragmentation in magnetite-treated cells compared to than control cells. Together, the present study reveals that magnetite exposure induces oxidative stress and depletes antioxidant levels in the cells to stimulate apoptotic pathway for cell death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Article  PubMed  CAS  Google Scholar 

  2. Salata OV (2004) Applications of nanoparticles in biology and medicine. J Nanobiotechnol 2:3

    Article  Google Scholar 

  3. Inoue K, Takano H, Yanagisawa R et al (2005) Effects of airway exposure to nanoparticles on lung inflammation induced by bacterial endotoxin in mice. Environ Health Perspect 114:1325–1330

    Article  Google Scholar 

  4. Olbrich C, Scholer N, Tabatt K, kayser O, Muller RH (2004) Cytotoxicity studies of Dynasan 114 solid lipid nanoparticles (SLN) on RAW 264.7 macrophages impact of phagocytosis on viability and cytokine production. J Pharm Pharmacol 56:883–891

    Article  PubMed  CAS  Google Scholar 

  5. Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ et al (2005) Am J Physiol Lung Cell Mol Physiol 289:L698–L708

    Article  PubMed  CAS  Google Scholar 

  6. Berry CC, Wells S, Charles S, Curtis ASG (2003) Dextran and albumin derivatised iron oxide nanoparticles: influence on fibroblasts in vitro. Biomaterials 24:4551–4557

    Article  PubMed  CAS  Google Scholar 

  7. Lacava LM, Lacava ZGM, Da Silva MF, Silva O, Chaves SB, Azevedo RB (2001) Magnetic resonance of a dextrancoated magnetic fluid intravenously administered in mice. Biophys J 80:2483–2486

    Article  PubMed  CAS  Google Scholar 

  8. Gupta AK, Curtis AS (2004) Surface modified superparamagnetic nanoparticles for drug delivery: interaction studies with human fibroblasts in culture. J Mater Sci Mater Med 15(4):493–496

    Article  PubMed  CAS  Google Scholar 

  9. Shubayev VI, Pisanic TR, Jin S (2009) Magnetic nanoparticles for theragnostics. Adv Drug Delivery Rev 61:467–477

    Article  CAS  Google Scholar 

  10. Cornelis K, Hurlburt CS (1977) Manual of mineralogy. Wiley, New York

    Google Scholar 

  11. Kwei GH, von Dreele RB, Williams A, Goldstone JA, Lawson AC II, Warburton WK (1990) Structure and valence from complementary anomalous X-ray and neutron powder diffraction. J Molecul Struct 223:383–406

    Article  CAS  Google Scholar 

  12. Perez JM, Simeone FJ, Saeki Y, Josephson L, Weissleder R (2003) Viral induced self-assembly of magnetic nanoparticles allows the detection of viral particles in biological media. J Am Chem Soc 125:10192–10193

    Article  PubMed  CAS  Google Scholar 

  13. Song Q, Zhang ZJ (2004) Shape control and associated magnetic properties of spinel cobalt ferrite nanocrystals. J Am Chem Soc 126:6164–6168

    Article  PubMed  CAS  Google Scholar 

  14. Li W, Ma N, Ong LL et al (2008) Enhanced thoracic gene delivery by magnetic nanobead-mediated vector. J Gene Med 10:897–909

    Article  PubMed  CAS  Google Scholar 

  15. Kim JS, Yoon TJ, Yu KN, Kim BG, Park SJ, Kim HW (2006) Toxicity and tissue distribution of magnetic nanoparticles in mice. Toxicol Sci 89:338–347

    Article  PubMed  CAS  Google Scholar 

  16. Hafeli UO, Pauer GJ (1999) In vitro and in vivo toxicity of magnetic microspheres. J Magn Magn Mater 194:76–82

    Article  CAS  Google Scholar 

  17. Garcia MP, Parca RM, Chaves SB, Silva LP, Santos AD, Lacava ZGM (2005) Morphological analysis of mouse lungs after treatment with magnetite-based magnetic fluid stabilized with DMSA. J Magn Magn Mater 293:277–282

    Article  CAS  Google Scholar 

  18. Ravichandran P, Periyakaruppan A, Sadanandan B, Ramesh V, Hall JC, Jejelowo O, Ramesh GT (2009) Induction of apoptosis in rat lung epithelial cells by multiwalled carbon nanotubes. J Biochem Mol Toxicol 23:333–334

    Article  PubMed  CAS  Google Scholar 

  19. Manna SK, Sarkar S, Barr J, Wise K, Barrera EV, Jejelowo O, Rice-Ficht AC, Ramesh GT (2005) Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes. Nano Lett 5:1676–1684

    Article  PubMed  CAS  Google Scholar 

  20. Gopikrishnan R, Zhang K, Ravichandran P, Biradar S, Ramesh V, Goornavar V, Jeffers RB, Pradhan A, Hall JC, Baluchamy S, Ramesh GT (2011) Epitaxial growth of the zinc oxide nanorods, their characterization and in vitro biocompatibility studies. J Mater Sci Mater Med. doi 10.1007/s10856-011-4405-5

  21. Sharma CS, Sarkar S, Periyakaruppan A, Barr J, Wise K, Thomas R, Wilson BL, Ramesh GT (2007) Single-walled carbon nanotubes induces oxidative stress in rat lung epithelial cells. J Nanosci Nanotechnol 7:2466–2472

    Article  PubMed  CAS  Google Scholar 

  22. Periakaruppan A, Kumar F, Sarkar S, Sharma CS, Ramesh GT (2007) Uranium induces oxidative stress in lung epithelial cells. Arch Toxicol 81:389–395

    Article  Google Scholar 

  23. Baluchamy S, Ravichandran P, Periakaruppan A, Ramesh V, Hall J, Zhang Y, Gridle S, Wu H, Ramesh GT (2010) Induction of cell death through alteration of oxidants and antioxidants in lung epithelial cells exposed to high energy protons. J Biol Chem 285:24769–24774

    Article  PubMed  CAS  Google Scholar 

  24. Periyakaruppan A, Sarkar S, Ravichandran P, Sadanandan B, Sharma CS, Ramesh V, Hall JC, Thomas R, Wilson BL, Ramesh GT (2009) Uranium induces apoptosis in lung epithelial cells. Arch Toxicol 83:595–600

    Article  PubMed  CAS  Google Scholar 

  25. Ravichandran P, Baluchamy S, Sadanandan B, Gopikrishnan R, Biradar S, Ramesh V, Hall JC, Ramesh GT (2010) Multiwalled carbon nanotubes activate NF-кB and AP-1 signaling pathways to induce apoptosis in rat lung epithelial cells. Apoptosis 15:1507–1516

    Article  PubMed  CAS  Google Scholar 

  26. Itoh H, Sugimoto T (2003) Systematic control of size, shape, structure, and magnetic properties of uniform magnetite and maghemite particles. J Colloid Interface Sci 265:283–295

    Article  PubMed  CAS  Google Scholar 

  27. Voit W, Kim DK, Zapka W, Muhammed M, Rao KV (2001) Magnetic behavior of coated superparamagnetic iron oxide nanoparticles in ferrofluids. Mater Res Soc 676:781–786

    Article  Google Scholar 

  28. Huang M, Khor E, Lim LY (2004) Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm Res 21:344–353

    Article  PubMed  CAS  Google Scholar 

  29. Warheit DB (2004) Nanoparticles: Health impacts? Mater Today 7:32–35

    Article  CAS  Google Scholar 

  30. Nel A, Xia T, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627

    Article  PubMed  CAS  Google Scholar 

  31. Berry CC, Wells S, Charles S, Aitchison G, Curtis AS (2004) Cell response to dextran and albumin derivatised iron oxide nanoparticles post internalization. Biomaterials 25:5405–5413

    Article  PubMed  CAS  Google Scholar 

  32. Apopa PL, Qian Y, Shao R, Guo NL, Schwegler-Berry D, Pacurari M, Porter D, Shi X, Vallyathan V, Castranova V, Flynn DC (2009) Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling. Part Fibre Toxicol 6:1

    Article  PubMed  Google Scholar 

  33. Manna SK, Rangasamy T, Wise K, Sarkar S, Shishodia S, Biswal S, Ramesh GT (2006) Long term environmental tobacco smoke activates nuclear transcription factor-kappa B, activator protein-1, and stress responsive kinases in mouse brain. Biochem Pharmacol 71:1602–1609

    Article  PubMed  CAS  Google Scholar 

  34. Rice-Evans C, Burdon R (1993) Free radical-lipid interactions and their pathological consequences. Prog Lipid Res 32:71–110

    Article  PubMed  CAS  Google Scholar 

  35. Riley PA (1994) Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 65:27–33

    Article  PubMed  CAS  Google Scholar 

  36. Podia M, Grundmann-Kollmann M (2001) Low molecular weight antioxidants and their role in skin ageing. Clin Exp Dermatol 26:578–582

    Article  Google Scholar 

  37. Sardesai VM (1995) Role of antioxidants in health maintenance. Nutr Clin Pract 10:19–25

    Article  PubMed  CAS  Google Scholar 

  38. Zhao Y, Kiningham KK, Lin SM, St Clair DK (2001) Over expression of MnSOD protects murine fibrosarcoma cells (FSa-II) from apoptosis and promotes a differentiation program upon treatment with 5-Azacytidine: involvement of MAPK and NFκB Pathways. Antioxid Redox Signal 3:375–386

    Article  PubMed  CAS  Google Scholar 

  39. Dominguez-Rodriguez IR, Gomez-Contreras PC, Hernandez-Flores G, Lerma-Diaz JM, Carranco A, Cervantes-Munguia R, Orbach-Arbouys S, Bravo-Cuella A (2001) In vivo inhibition by antioxidants of adriamycin-induced apoptosis in murine peritoneal macrophages. Anti Cancer Res 21:1869–1872

    CAS  Google Scholar 

  40. Shi YG (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell 9:459–470

    Article  PubMed  CAS  Google Scholar 

  41. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, Raju SM, Smulson ME, Yamin TT, Yu VL, Miller DK (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43

    Article  PubMed  CAS  Google Scholar 

  42. Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116(2):205–219

    Article  PubMed  CAS  Google Scholar 

  43. Patlolla A, Patlolla B, Tchounwou P (2010) Evaluation of cell viability, DNA damage, and cell death in normal human dermal fibroblast cells induced by functionalized multiwalled carbon nanotubes. Mol Cell Biochem 338:225–232

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by NIH funding NIH 1P20MD001822-1.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph C. Hall.

Additional information

An erratum to this article can be found online at http://dx.doi.org/10.1007/s11010-013-1596-8.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramesh, V., Ravichandran, P., Copeland, C.L. et al. Magnetite induces oxidative stress and apoptosis in lung epithelial cells. Mol Cell Biochem 363, 225–234 (2012). https://doi.org/10.1007/s11010-011-1174-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-1174-x

Keywords

Navigation