Skip to main content
SpringerLink
Log in

Cytotoxicity Analysis of Morphologically Different Sol-Gel-Synthesized MgO Nanoparticles and Their In Vitro Insulin Resistance Reversal Ability in Adipose cells

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Insulin resistance is one of the major factors that leads to type 2 diabetes. Although insulin therapies have been shown to overcome insulin resistance, overweight and hypoglycemia are still observed in most cases. The disadvantages of insulin therapies have driven the interest in developing novel curative agents with enhanced insulin resistance reversibility. Magnesium deficiency has also been recognized as a common problem which leads to insulin resistance in both type 1 and 2 diabetes. Oxide nanoparticles demonstrate highly tunable physicochemical properties that can be exploited by engineers to develop unique oxide nanoparticles for tailored applications. Magnesium supplements for diabetic cells have been reported to increase the insulin resistance reversibility. Hence, it is hypothesized that magnesium oxide (MgO) nanoparticles could be molecularly engineered to offer enhanced therapeutic efficacy in reversing insulin resistance. In the present work, morphologically different MgO nanoparticles were synthesized and evaluated for biophysical characteristics, biocompatibility, cytotoxicity, and insulin resistance reversibility. MTT assay revealed that hexagonally shaped MgO nanoparticles are less toxic to 3T3-L1 adipose cells (diabetic) compared with spherically and rod-shaped MgO nanoparticles. MTT assays using VERO cells (normal, non-diabetic) showed that 400 μg/ml of hexagonal MgO nanoparticles were less toxic to both diabetic and non-diabetic cells. DNS glucose assay and western blot showed that hexagonally shaped MgO nanoparticles had reversed 29.5% of insulin resistance whilst fluorescence microscopy studies indicated that the insulin resistance reversal is due to the activation of intracellular enzymes. The probable mechanism for MgO nanoparticles to induce cytotoxic effect and insulin resistance reversal is discussed.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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. Zimmet, P. (2000). Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted? Journal of Internal Medicine, 247(3), 301–310.

    CAS  PubMed  Google Scholar 

  2. Teixeira-Lemos, E., Nunes, S., Teixeira, F., & Reis, F. (2011). Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovascular Diabetology, 10(1), 12.

    PubMed  PubMed Central  Google Scholar 

  3. World Health Organization. (2016). Global report on diabetes: executive summary (No. WHO/NMH/NVI/16.3). https://apps.who.int/iris/handle/10665/204874.

  4. Cho, N. H., Shaw, J. E., Karuranga, S., Huang, Y., da Rocha Fernandes, J. D., Ohlrogge, A. W., & Malanda, B. (2018). IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Research and Clinical Practice, 138, 271–281.

    CAS  PubMed  Google Scholar 

  5. Federation ID, (2015). IDF Diabetes Atlas. 7th edn. Brussels, Belgium: International Diabetes Federation. https://suckhoenoitiet.vn/download/Atla-benh-dai-thao-duong-2-1511669800.pdf.

  6. Surugue, L. (2016). World Health Day 2016: 422 million people live with diabetes worldwide. International Business Times. https://www.ibtimes.co.uk/world-health-day-2016-422-million-people-live-diabetes-worldwide-1553465.

  7. Rosenbloom, A. L., Joe, J. R., Young, R. S., & Winter, W. E. (1999). Emerging epidemic of type 2 diabetes in youth. Diabetes Care, 22(2), 345–354.

    CAS  PubMed  Google Scholar 

  8. Honardoost, M., Reza Sarookhani, M., Arefian, E., & Soleimani, M. (2014). Insulin resistance associated genes and miRNAs. Applied Biochemistry and Biotechnology, 174(1), 63–80. https://doi.org/10.1007/s12010-014-1014-z.

    Article  CAS  PubMed  Google Scholar 

  9. D’Eliseo, P., Blaauw, J., Milicevic, J., Wyatt, J., Ignaut, D., & Malone, J. (2000). Patient acceptability of a new 3.0 ml pre-filled insulin pen. Current Medical Research and Opinion, 16(2), 125–133.

    PubMed  Google Scholar 

  10. Hirsch, I. B. (2005). Insulin analogues. New England Journal of Medicine, 352(2), 174–183.

    CAS  PubMed  Google Scholar 

  11. Cochran, E., Musso, C., & Gorden, P. (2005). The use of U-500 in patients with extreme insulin resistance. Diabetes Care, 28(5), 1240–1244.

    CAS  PubMed  Google Scholar 

  12. Cochran, E., & Gorden, P. (2008). Use of U-500 insulin in the treatment of severe insulin resistance. Insulin, 3(4), 211–218.

    Google Scholar 

  13. Swinnen, S. G., Hoekstra, J. B., & DeVries, J. H. (2009). Insulin therapy for type 2 diabetes. Diabetes Care, 32(suppl 2), S253–S259.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Hypoglycemia Cryer, P., Fisher, J., & Shamoon, H. (1994). Hypoglycemia (Technical Review). Diabetes Care, 17, 734–755.

    PubMed  Google Scholar 

  15. Ryan, M., Livingstone, M. B. E., Ducluzeau, P.-H., Sallé, A., Genaitay, M., & Ritz, P. (2008). Is a failure to recognize an increase in food intake a key to understanding insulin-induced weight gain? Diabetes Care, 31(3), 448–450.

    PubMed  Google Scholar 

  16. Hassan, H. A., & El-Gharib, N. E. (2015). Obesity and clinical riskiness relationship: therapeutic management by dietary antioxidant supplementation—a review. Applied Biochemistry and Biotechnology, 176(3), 647–669. https://doi.org/10.1007/s12010-015-1602-6.

    Article  CAS  PubMed  Google Scholar 

  17. Beran, D., Ewen, M., & Laing, R. (2016). Insulin in 2016: challenge and constraints to access. Diabetes research and clinical practice, 117, 119–121.

  18. Putakala, M., Gujjala, S., Nukala, S., & Desireddy, S. (2017). Beneficial effects of phyllanthus amarus against high fructose diet induced insulin resistance and hepatic oxidative stress in male wistar rats. Applied Biochemistry and Biotechnology, 183(3), 744–764. https://doi.org/10.1007/s12010-017-2461-0.

    Article  CAS  PubMed  Google Scholar 

  19. Vanroelen, W. F., Van Gaal, L. F., Van Rooy, P. E., & de Leeuw, I. H. (1985). Serum and erythrocyte magnesium levels in type I and type II diabetics. Acta Diabetologica, 22(3), 185–190.

    CAS  Google Scholar 

  20. Mather, H., Nisbet, J. A., Burton, G., Poston, G., Bland, J., Bailey, P. A., & Pilkington, T. (1979). Hypomagnesaemia in diabetes. Clinica Chimica Acta, 95(2), 235–242.

    CAS  Google Scholar 

  21. Sjögren, A., Florén, C. H., & Nilsson, Å. (1988). Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus. Acta Medica Scandinavica, 224(5), 461–466.

    PubMed  Google Scholar 

  22. Moles, K. W., & McMullen, J. K. (1982). Insulin resistance and hypomagnesaemia: case report. British Medical Journal (Clinical Research Ed.), 285(6337), 262.

    CAS  Google Scholar 

  23. Durlach, J., & Rayssiguier, Y. (1983). Données nouvelles sur les relations entre magnésium et hydrates de carbone. II: Données cliniques et thérapeutiques. Magnesium, 2(4-6), 192–224.

    CAS  Google Scholar 

  24. Kandeel, F. R., Balon, E., Scott, S., & Nadler, J. L. (1996). Magnesium deficiency and glucose metabolism in rat adipocytes. Metabolism, 45(7), 838–843.

    CAS  PubMed  Google Scholar 

  25. Maier, J. A., Malpuech-Brugère, C., Zimowska, W., Rayssiguier, Y., & Mazur, A. (2004). Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1689(1), 13–21.

    CAS  Google Scholar 

  26. Swaminathan, R. (2003). Magnesium metabolism and its disorders. The Clinical Biochemist Reviews, 24(2), 47–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Jeevanandam, J., Chan, Y. S., & Danquah, M. K. (2017). Calcination-dependent morphology transformation of sol-gel- synthesized MgO nanoparticles. Chemistry Select, 2(32), 10393–10404.

    CAS  Google Scholar 

  28. Jeevanandam, J., Danquah, K., Debnath, M., Meka, V. S., & Chan, Y. S. (2015). Opportunities for nano-formulations in type 2 diabetes mellitus treatments. Current Pharmaceutical Biotechnology, 16(10), 853–870.

    CAS  PubMed  Google Scholar 

  29. Rajagopalan, S., Koper, O., Decker, S., & Klabunde, K. J. (2002). Nanocrystalline metal oxides as destructive adsorbents for organophosphorus compounds at ambient temperatures. Chemistry--A European Journal, 8(11), 2602–2607.

    CAS  Google Scholar 

  30. Choudary, B. M., Mulukutla, R. S., & Klabunde, K. J. (2003). Benzylation of aromatic compounds with different crystallites of MgO. Journal of the American Chemical Society, 125(8), 2020–2021.

    CAS  PubMed  Google Scholar 

  31. Stark, J. V., & Klabunde, K. J. (1996). Nanoscale metal oxide particles/clusters as chemical reagents. Adsorption of hydrogen halides, nitric oxide, and sulfur trioxide on magnesium oxide nanocrystals and compared with microcrystals. Chemistry of Materials, 8(8), 1913–1918.

    CAS  Google Scholar 

  32. Li, W.-C., Lu, A.-H., Weidenthaler, C., & Schüth, F. (2004). Hard-templating pathway to create mesoporous magnesium oxide. Chemistry of Materials, 16(26), 5676–5681.

    CAS  Google Scholar 

  33. Kumar, A., & Kumar, J. (2008). On the synthesis and optical absorption studies of nano-size magnesium oxide powder. Journal of Physics and Chemistry of Solids, 69(11), 2764–2772.

    CAS  Google Scholar 

  34. Hattori, H. (1995). Heterogeneous basic catalysis. Chemical Reviews, 95(3), 537–558.

    CAS  Google Scholar 

  35. Xu, B.-Q., Wei, J.-M., Wang, H.-Y., Sun, K.-Q., & Zhu, Q.-M. (2001). Nano-MgO: novel preparation and application as support of Ni catalyst for CO 2 reforming of methane. Catalysis Today, 68(1), 217–225.

    CAS  Google Scholar 

  36. Koper, O. B., Lagadic, I., Volodin, A., & Klabunde, K. J. (1997). Alkaline-earth oxide nanoparticles obtained by aerogel methods. Characterization and rational for unexpectedly high surface chemical reactivities. Chemistry of Materials, 9(11), 2468–2480.

    CAS  Google Scholar 

  37. Klabunde, K. J., Stark, J., Koper, O., Mohs, C., Park, D. G., Decker, S., Jiang, Y., Lagadic, I., & Zhang, D. (1996). Nanocrystals as stoichiometric reagents with unique surface chemistry. The Journal of Physical Chemistry, 100(30), 12142–12153.

    CAS  Google Scholar 

  38. McKenna, K. P., Koller, D., Sternig, A., Siedl, N., Govind, N., Sushko, P. V., & Diwald, O. (2011). Optical properties of nanocrystal interfaces in compressed MgO nanopowders. ACS Nano, 5(4), 3003–3009.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Krishnamoorthy, K., Manivannan, G., Kim, S. J., Jeyasubramanian, K., & Premanathan, M. (2012). Antibacterial activity of MgO nanoparticles based on lipid peroxidation by oxygen vacancy. Journal of Nanoparticle Research, 14(9), 1063.

    Google Scholar 

  40. Sawai, J., & Yoshikawa, T. (2004). Quantitative evaluation of antifungal activity of metallic oxide powders (MgO, CaO and ZnO) by an indirect conductimetric assay. Journal of Applied Microbiology, 96(4), 803–809.

    CAS  PubMed  Google Scholar 

  41. Krishnamoorthy, K., Moon, J. Y., Hyun, H. B., Cho, S. K., & Kim, S.-J. (2012). Mechanistic investigation on the toxicity of MgO nanoparticles toward cancer cells. Journal of Materials Chemistry, 22(47), 24610–24617.

    CAS  Google Scholar 

  42. Bertinetti, L., Drouet, C., Combes, C., Rey, C., Tampieri, A., Coluccia, S., & Martra, G. (2009). Surface characteristics of nanocrystalline apatites: effect of Mg surface enrichment on morphology, surface hydration species, and cationic environments. Langmuir, 25(10), 5647–5654.

    CAS  PubMed  Google Scholar 

  43. Jeevanandam, J., San Chan, Y., & Danquah, M. K. (2016). Nano-formulations of drugs: recent developments, impact and challenges. Biochimie, 128, 99–112.

    PubMed  Google Scholar 

  44. He, A., Zhu, L., Gupta, N., Chang, Y., & Fang, F. (2007). Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3 T3-L1 adipocytes. Molecular Endocrinology, 21(11), 2785–2794.

    CAS  PubMed  Google Scholar 

  45. Schubert, U. (2015). Chemistry and fundamentals of the sol–gel process. The Sol-Gel Handbook-Synthesis, Characterization, and Applications: Synthesis, Characterization and Applications, 3-Volume Set,1-28.

  46. Jaison, J., Balakumar, S., Chan, Y. (2015). Sol–Gel synthesis and characterization of magnesium peroxide nanoparticles. In: IOP Conference Series: Materials Science and Engineering, vol 1. IOP Publishing, p 012005

  47. McGillicuddy, F. C., Harford, K. A., Reynolds, C. M., Oliver, E., Claessens, M., Mills, K. H. G., Roche, H. M. (2011) Lack of interleukin-1 receptor I (IL-1RI) protects mice from high-fat diet-induced adipose tissue inflammation coincident with improved glucose homeostasis. Diabetes, 60(6), 1688–1698

  48. Carmichael, J., DeGraff, W. G., Gazdar, A. F., Minna, J. D., & Mitchell, J. B. (1987). Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Research, 47(4), 936–942.

    CAS  PubMed  Google Scholar 

  49. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65(1-2), 55–63.

    CAS  PubMed  Google Scholar 

  50. Mohamed, S. A., Al-Malki, A. L., & Kumosani, T. A. (2009). Partial purification and characterization of five α-amylases from a wheat local variety (Balady) during germination. Australian Journal of Basic and Applied Sciences, 3, 1740–1748.

    CAS  Google Scholar 

  51. Moon, J. Y., Mosaddik, A., Kim, H., Cho, M., Choi, H.-K., Kim, Y. S., & Cho, S. K. (2011). The chloroform fraction of guava (Psidium cattleianum sabine) leaf extract inhibits human gastric cancer cell proliferation via induction of apoptosis. Food Chemistry, 125(2), 369–375.

    CAS  Google Scholar 

  52. Zak, A. K., Abrishami, M. E., Majid, W. A., Yousefi, R., & Hosseini, S. (2011). Effects of annealing temperature on some structural and optical properties of ZnO nanoparticles prepared by a modified sol–gel combustion method. Ceramics International, 37(1), 393–398.

    CAS  Google Scholar 

  53. Lauritsen, J., Bollinger, M., Lægsgaard, E., Jacobsen, K. W., Nørskov, J. K., Clausen, B., Topsøe, H., & Besenbacher, F. (2004). Atomic-scale insight into structure and morphology changes of MoS2 nanoclusters in hydrotreating catalysts. Journal of Catalysis, 221(2), 510–522.

    CAS  Google Scholar 

  54. Präbst, K., Engelhardt, H., Ringgeler, S., & Hübner, H. (2017). Basic colorimetric proliferation assays: MTT, WST, and resazurin. In Cell Viability Assays (pp. 1-17). Humana Press, New York, NY.

  55. Mao, Z., Xu, B., Ji, X., Zhou, K., Zhang, X., Chen, M., Han, X., Tang, Q., Wang, X., & Xia, Y. (2015). Titanium dioxide nanoparticles alter cellular morphology via disturbing the microtubule dynamics. Nanoscale, 7(18), 8466–8475.

    CAS  PubMed  Google Scholar 

  56. Duan, J., Yu, Y., Li, Y., Yu, Y., Li, Y., Zhou, X., Huang, P., & Sun, Z. (2013). Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint. PLoS One, 8(4), e62087.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Favaretto, F., Milan, G., Collin, G. B., Marshall, J. D., Stasi, F., Maffei, P., Vettor, R., & Naggert, J. K. (2014). GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance. PLoS One, 9(10), e109540.

    PubMed  PubMed Central  Google Scholar 

  58. Cushman, S., & Wardzala, L. (1980). Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. Journal of Biological Chemistry, 255(10), 4758–4762.

    CAS  PubMed  Google Scholar 

  59. Jaldin-Fincati, J. R., Pavarotti, M., Frendo-Cumbo, S., Bilan, P. J., & Klip, A. (2017). Update on GLUT4 vesicle traffic: a cornerstone of insulin action. Trends in Endocrinology and Metabolism, 28(8), 597–611.

    CAS  PubMed  Google Scholar 

  60. Sonksen, P., & Sonksen, J. (2000). Insulin: understanding its action in health and disease. British Journal of Anaesthesia, 85(1), 69–79.

    CAS  PubMed  Google Scholar 

  61. Stöckli, J., Fazakerley, D. J., & James, D. E. (2011). GLUT4 exocytosis. Journal of Cell Science, 124(24), 4147–4159.

    PubMed  PubMed Central  Google Scholar 

  62. Martin, O. J., Lee, A., & McGraw, T. E. (2006). GLUT4 distribution between the plasma membrane and the intracellular compartments is maintained by an insulin-modulated bipartite dynamic mechanism. Journal of Biological Chemistry, 281(1), 484–490.

    CAS  PubMed  Google Scholar 

  63. Riccardi, C., & Nicoletti, I. (2006). Analysis of apoptosis by propidium iodide staining and flow cytometry. Nature Protocols, 1(3), 1458–1461.

    CAS  PubMed  Google Scholar 

  64. Cousin, B., Munoz, O., André, M., Fontanilles, A., Dani, C., Cousin, J., Laharrague, P., Casteilla, L., & Enicaud, L. (1999). A role for preadipocytes as macrophage-like cells. The FASEB Journal, 13(2), 305–312.

    CAS  PubMed  Google Scholar 

  65. Huang, D.-M., Hung, Y., Ko, B.-S., Hsu, S.-C., Chen, W.-H., Chien, C.-L., Tsai, C.-P., Kuo, C.-T., Kang, J.-C., & Yang, C.-S. (2005). Highly efficient cellular labeling of mesoporous nanoparticles in human mesenchymal stem cells: implication for stem cell tracking. The FASEB Journal, 19(14), 2014–2016.

    CAS  PubMed  Google Scholar 

  66. Uboldi, C., Giudetti, G., Broggi, F., Gilliland, D., Ponti, J., & Rossi, F. (2012). Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3 T3 mouse fibroblasts. Mutation Research, Genetic Toxicology and Environmental Mutagenesis, 745(1), 11–20.

    CAS  Google Scholar 

  67. Shimkunas, R. A., Robinson, E., Lam, R., Lu, S., Xu, X., Zhang, X.-Q., Huang, H., Osawa, E., & Ho, D. (2009). Nanodiamond–insulin complexes as pH-dependent protein delivery vehicles. Biomaterials, 30(29), 5720–5728.

    CAS  PubMed  Google Scholar 

  68. Pandurangan, M., Veerappan, M., & Kim, D. H. (2015). Cytotoxicity of zinc oxide nanoparticles on antioxidant enzyme activities and mRNA expression in the cocultured C2C12 and 3 T3-L1 cells. Applied Biochemistry and Biotechnology, 175(3), 1270–1280.

    CAS  PubMed  Google Scholar 

  69. Chung, T.-H., Wu, S.-H., Yao, M., Lu, C.-W., Lin, Y.-S., Hung, Y., Mou, C.-Y., Chen, Y.-C., & Huang, D.-M. (2007). The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3 T3-L1 cells and human mesenchymal stem cells. Biomaterials, 28(19), 2959–2966.

    CAS  PubMed  Google Scholar 

  70. Verma, A., & Stellacci, F. (2010). Effect of surface properties on nanoparticle–cell interactions. Small, 6(1), 12–21.

    CAS  PubMed  Google Scholar 

  71. Hussain, S., Hess, K., Gearhart, J., Geiss, K., & Schlager, J. (2005). In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicology In Vitro, 19(7), 975–983.

    CAS  PubMed  Google Scholar 

  72. Ayyub, P., Palkar, V., Chattopadhyay, S., & Multani, M. (1995). Effect of crystal size reduction on lattice symmetry and cooperative properties. Physical Review B, 51(9), 6135.

    CAS  Google Scholar 

  73. Helveg, S., Lauritsen, J. V., Lægsgaard, E., Stensgaard, I., Nørskov, J. K., Clausen, B., Topsøe, H., & Besenbacher, F. (2000). Atomic-scale structure of single-layer MoS 2 nanoclusters. Physical Review Letters, 84(5), 951–954.

    CAS  PubMed  Google Scholar 

  74. Xu, L., Hong, M., Yang, Y., Cui, J., & Li, C. (2016). Synthesis, structural characterization, in vitro cytotoxicities, and BSA interaction of di-organotin(IV) complexes derived from salicylaldehyde nicotinoyl hydrazone. Journal of Coordination Chemistry, 69(17), 2598–2609. https://doi.org/10.1080/00958972.2016.1217408.

    Article  CAS  Google Scholar 

  75. Yue, Y., Li, X., Sigg, L., Suter, M. J., Pillai, S., Behra, R., & Schirmer, K. (2017). Interaction of silver nanoparticles with algae and fish cells: a side by side comparison. Journal of Nanobiotechnology, 15(1), 16.

    PubMed  PubMed Central  Google Scholar 

  76. Yin, Y., Hu, Z., Du, W., Ai, F., Ji, R., Gardea-Torresdey, J. L., & Guo, H. (2017). Elevated CO 2 levels increase the toxicity of ZnO nanoparticles to goldfish (Carassius auratus) in a water-sediment ecosystem. Journal of Hazardous Materials, 327, 64–70.

    CAS  PubMed  Google Scholar 

  77. Chueh, P. J., Liang, R.-Y., Lee, Y.-H., Zeng, Z.-M., & Chuang, S.-M. (2014). Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines. Journal of Hazardous Materials, 264, 303–312.

    CAS  PubMed  Google Scholar 

  78. Su, C.-H., Sheu, H.-S., Lin, C.-Y., Huang, C.-C., Lo, Y.-W., Pu, Y.-C., Weng, J.-C., Shieh, D.-B., Chen, J.-H., & Yeh, C.-S. (2007). Nanoshell magnetic resonance imaging contrast agents. Journal of the American Chemical Society, 129(7), 2139–2146.

    CAS  PubMed  Google Scholar 

  79. Sasidharan, A., Panchakarla, L., Chandran, P., Menon, D., Nair, S., Rao, C., & Koyakutty, M. (2011). Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene. Nanoscale, 3(6), 2461–2464.

    CAS  PubMed  Google Scholar 

  80. Balaji, S., Mandal, B. K., Ranjan, S., Dasgupta, N., Chidambaram, R. (2017). Nano-zirconia–Evaluation of its antioxidant and anticancer activity. Journal of Photochemistry and Photobiology B: Biology. 170, 125–133.

  81. Szalay, B., Tátrai, E., Nyírő, G., Vezér, T., & Dura, G. (2012). Potential toxic effects of iron oxide nanoparticles in in vivo and in vitro experiments. Journal of Applied Toxicology, 32(6), 446–453.

    CAS  PubMed  Google Scholar 

  82. Xiao, K., Li, Y., Luo, J., Lee, J. S., Xiao, W., Gonik, A. M., Agarwal, R. G., & Lam, K. S. (2011). The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles. Biomaterials, 32(13), 3435–3446.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Alexis, F., Pridgen, E., Molnar, L. K., & Farokhzad, O. C. (2008). Factors affecting the clearance and biodistribution of polymeric nanoparticles. Molecular Pharmaceutics, 5(4), 505–515.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Yamamoto, Y., Nagasaki, Y., Kato, Y., Sugiyama, Y., & Kataoka, K. (2001). Long-circulating poly (ethylene glycol)–poly (d, l-lactide) block copolymer micelles with modulated surface charge. Journal of Controlled Release, 77(1), 27–38.

    CAS  PubMed  Google Scholar 

  85. Fröhlich, E. (2012). The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. International Journal of Nanomedicine, 7(1), 5577–5591.

    PubMed  PubMed Central  Google Scholar 

  86. Andelman, T., Gordonov, S., Busto, G., Moghe, P. V., & Riman, R. E. (2010). Synthesis and cytotoxicity of Y2O3 nanoparticles of various morphologies. Nanoscale Research Letters, 5(2), 263.

    CAS  Google Scholar 

  87. Murgia, S., Falchi, A. M., Mano, M., Lampis, S., Angius, R., Carnerup, A. M., Schmidt, J., Diaz, G., Giacca, M., & Talmon, Y. (2010). Nanoparticles from lipid-based liquid crystals: emulsifier influence on morphology and cytotoxicity. The Journal of Physical Chemistry B, 114(10), 3518–3525.

    CAS  PubMed  Google Scholar 

  88. Kim, T. H., Kim, M., Park, H. S., Shin, U. S., Gong, M. S., & Kim, H. W. (2012). Size-dependent cellular toxicity of silver nanoparticles. Journal of Biomedical Materials Research Part A, 100(4), 1033–1043.

    PubMed  Google Scholar 

  89. Ryabchikova, E. I., Mazurkova, N. A., Shikina, N. V., Ismagilov, Z. R. (2010). The crystalline forms of titanium dioxide nanoparticles affect their interactions with individual cells. Journal of Medical Chemical, Biological and Radiological Defense, http://www.jmedcbr.org/issue_0801/Ryabchikova/Ryabchikova_Nano_10_2010.html.

  90. Draeger, A., Monastyrskaya, K., & Babiychuk, E. B. (2011). Plasma membrane repair and cellular damage control: the annexin survival kit. Biochemical Pharmacology, 81(6), 703–712.

    CAS  PubMed  Google Scholar 

  91. Wang, T., Bai, J., Jiang, X., & Nienhaus, G. U. (2012). Cellular uptake of nanoparticles by membrane penetration: a study combining confocal microscopy with FTIR spectroelectrochemistry. ACS Nano, 6(2), 1251–1259.

    CAS  PubMed  Google Scholar 

  92. Mellgren, R. L. (2011). A new twist on plasma membrane repair. Communicative & Integrative Biology, 4(2), 198–200.

    CAS  Google Scholar 

  93. Kohn, A. D., Summers, S. A., Birnbaum, M. J., & Roth, R. A. (1996). Expression of a constitutively active Akt Ser/Thr kinase in 3 T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. Journal of Biological Chemistry, 271(49), 31372–31378.

    CAS  PubMed  Google Scholar 

  94. Ito, A., Shinkai, M., Honda, H., & Kobayashi, T. (2005). Medical application of functionalized magnetic nanoparticles. Journal of Bioscience and Bioengineering, 100(1), 1–11.

    CAS  PubMed  Google Scholar 

  95. Lovrić, J., Cho, S. J., Winnik, F. M., & Maysinger, D. (2005). Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chemistry & Biology, 12(11), 1227–1234.

    Google Scholar 

  96. Green, D. R., & Kroemer, G. (2004). The pathophysiology of mitochondrial cell death. Science, 305(5684), 626–629.

    CAS  PubMed  Google Scholar 

  97. Tait, S. W., & Green, D. R. (2010). Mitochondria and cell death: outer membrane permeabilization and beyond. Nature Reviews Molecular Cell Biology, 11(9), 621–632.

    CAS  PubMed  Google Scholar 

  98. Annunziato, L., Amoroso, S., Pannaccione, A., Cataldi, M., Pignataro, G., D’Alessio, A., Sirabella, R., Secondo, A., Sibaud, L., & Di Renzo, G. (2003). Apoptosis induced in neuronal cells by oxidative stress: role played by caspases and intracellular calcium ions. Toxicology Letters, 139(2), 125–133.

    CAS  PubMed  Google Scholar 

  99. Soenen, S. J., Rivera-Gil, P., Montenegro, J.-M., Parak, W. J., De Smedt, S. C., & Braeckmans, K. (2011). Cellular toxicity of inorganic nanoparticles: common aspects and guidelines for improved nanotoxicity evaluation. Nano Today, 6(5), 446–465.

    CAS  Google Scholar 

  100. Funnell, W. R. J., & Maysinger, D. (2006). Three-dimensional reconstruction of cell nuclei, internalized quantum dots and sites of lipid peroxidation. Journal of Nanobiotechnology, 4(1), 10.

    PubMed  PubMed Central  Google Scholar 

  101. Asati, A., Santra, S., Kaittanis, C., & Perez, J. M. (2010). Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano, 4(9), 5321–5331.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. AshaRani, P., Low Kah Mun, G., Hande, M. P., & Valiyaveettil, S. (2008). Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano, 3(2), 279–290.

    Google Scholar 

  103. Boyoglu, C., Boyoglu-Barnum, S., Soni, S., He, Q., Willing, G., Miller, M., & Singh, S. (2011). The intracellular co-localizations of different size of gold nanoparticles. Nanotechnology, 489–492.

  104. Zinchenko, A. A., Luckel, F., & Yoshikawa, K. (2007). Transcription of giant DNA complexed with cationic nanoparticles as a simple model of chromatin. Biophysical Journal, 92(4), 1318–1325.

    CAS  PubMed  Google Scholar 

  105. Chen, M., & von Mikecz, A. (2005). Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO 2 nanoparticles. Experimental Cell Research, 305(1), 51–62.

    CAS  PubMed  Google Scholar 

  106. Li, N., Ma, L., Wang, J., Zheng, L., Liu, J., Duan, Y., Liu, H., Zhao, X., Wang, S., & Wang, H. (2009). Interaction between nano-anatase TiO 2 and liver DNA from mice in vivo. Nanoscale Research Letters, 5(1), 108–115.

    PubMed  PubMed Central  Google Scholar 

  107. Nitin, N., LaConte, L., Rhee, W. J., & Bao, G. (2009). Tat peptide is capable of importing large nanoparticles across nuclear membrane in digitonin permeabilized cells. Annals of Biomedical Engineering, 37(10), 2018–2027.

    PubMed  PubMed Central  Google Scholar 

  108. Nabeshi, H., Yoshikawa, T., Arimori, A., Yoshida, T., Tochigi, S., Hirai, T., Akase, T., Nagano, K., Abe, Y., & Kamada, H. (2011). Effect of surface properties of silica nanoparticles on their cytotoxicity and cellular distribution in murine macrophages. Nanoscale Research Letters, 6(1), 1–6.

    Google Scholar 

  109. Peters, R. (2005). Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality. Traffic, 6(5), 421–427.

    CAS  PubMed  Google Scholar 

  110. Houstis, N. E. (2007) Reactive oxygen species play a causal role in multiple forms of insulin resistance. Doctoral dissertation, Massachusetts Institute of Technology.

  111. Pekala, P., Lane, M. D., Watkins, P. A., & Moss, J. (1981). On the mechanism of preadipocyte differentiation. Masking of poly (ADP-ribose) synthetase activity during differentiation of 3 T3-L1 preadipocytes. Journal of Biological Chemistry, 256(10), 4871–4876.

    CAS  PubMed  Google Scholar 

  112. Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature, 444(7121), 840–846.

    CAS  PubMed  Google Scholar 

  113. Kao, W. L., Folsom, A. R., Nieto, F. J., Mo, J.-P., Watson, R. L., & Brancati, F. L. (1999). Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Archives of Internal Medicine, 159(18), 2151–2159.

    CAS  PubMed  Google Scholar 

  114. Garland, H. (1992). New experimental data on the relationship between diabetes mellitus and magnesium. Magnesium Research, 5(3), 193–202.

    CAS  PubMed  Google Scholar 

  115. Schnack, C., Bauer, I., Pregant, P., Hopmeier, P., & Schernthaner, G. (1992). Hypomagnesaemia in type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control. Diabetologia, 35(1), 77–79.

    CAS  PubMed  Google Scholar 

  116. Resnick, L. M., Gupta, R. K., Bhargava, K. K., Gruenspan, H., Alderman, M. H., & Laragh, J. H. (1991). Cellular ions in hypertension, diabetes, and obesity. A nuclear magnetic resonance spectroscopic study. Hypertension, 17(6 Pt 2), 951–957.

    CAS  PubMed  Google Scholar 

  117. Barbagallo, M., Gupta, R. K., Dominguez, L. J., & Resnick, L. M. (2000). Cellular ionic alterations with age: relation to hypertension and diabetes. Journal of the American Geriatrics Society, 48(9), 1111–1116.

    CAS  PubMed  Google Scholar 

  118. Barbagallo, M., Resnick, L. M. (1996) Calcium and magnesium in the regulation of smooth muscle function and blood pressure. In: Endocrinology of the Vasculature. Springer, pp 283-300

  119. Paolisso, G., & Barbagallo, M. (1997). Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium. American Journal of Hypertension, 10(3), 346–355.

    CAS  PubMed  Google Scholar 

  120. Barbagallo, M., Dominguez, L. J., Galioto, A., Ferlisi, A., Cani, C., Malfa, L., Pineo, A., & Paolisso, G. (2003). Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X. Molecular Aspects of Medicine, 24(1), 39–52.

    CAS  PubMed  Google Scholar 

  121. Zhang, Y., Chen, Y., Westerhoff, P., Hristovski, K., & Crittenden, J. C. (2008). Stability of commercial metal oxide nanoparticles in water. Water Research, 42(8-9), 2204–2212.

    CAS  PubMed  Google Scholar 

  122. Keller, A. A., Wang, H., Zhou, D., Lenihan, H. S., Cherr, G., Cardinale, B. J., Miller, R., & Ji, Z. (2010). Stability and aggregation of metal oxide nanoparticles in natural aqueous matrices. Environmental Science & Technology, 44(6), 1962–1967.

    CAS  Google Scholar 

  123. Zhong, L., Yu, Y., Lian, H.-Z., Hu, X., Fu, H., & Chen, Y.-J. (2017). Solubility of nano-sized metal oxides evaluated by using in vitro simulated lung and gastrointestinal fluids: implication for health risks. Journal of Nanoparticle Research, 19(11), 375.

    Google Scholar 

  124. Fernandez-Fernandez, A., Manchanda, R., & McGoron, A. J. (2011). Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms. Applied Biochemistry and Biotechnology, 165(7), 1628–1651. https://doi.org/10.1007/s12010-011-9383-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Sylow, L., Kleinert, M., Pehmøller, C., Prats, C., Chiu, T. T., Klip, A., Richter, E. A., & Jensen, T. E. (2014). Akt and Rac1 signaling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance. Cellular Signalling, 26(2), 323–331.

    CAS  PubMed  Google Scholar 

  126. Sylow, L., Jensen, T. E., Kleinert, M., Højlund, K., Kiens, B., Wojtaszewski, J., Prats, C., Schjerling, P., & Richter, E. A. (2013). Rac1 signaling is required for insulin-stimulated glucose uptake and is dysregulated in insulin-resistant murine and human skeletal muscle. Diabetes, 62(6), 1865–1875.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Kumar, R., Sharma, B., Tomar, N. R., Roy, P., Gupta, A. K., & Kumar, A. (2011). In vivo evalution of hypoglycemic activity of Aloe spp. and identification of its mode of action on GLUT-4 gene expression in vitro. Applied Biochemistry and Biotechnology, 164(8), 1246–1256. https://doi.org/10.1007/s12010-011-9210-6.

    Article  CAS  PubMed  Google Scholar 

  128. Etgen, G., Memon, A., Thompson, G., & Ivy, J. (1993). Insulin-and contraction-stimulated translocation of GTP-binding proteins and GLUT4 protein in skeletal muscle. Journal of Biological Chemistry, 268(27), 20164–20169.

    CAS  PubMed  Google Scholar 

  129. Nel, A. E., Mädler, L., Velegol, D., Xia, T., Hoek, E. M., Somasundaran, P., Klaessig, F., Castranova, V., & Thompson, M. (2009). Understanding biophysicochemical interactions at the nano-bio interface. Nature Materials, 8(7), 543–557.

    CAS  PubMed  Google Scholar 

  130. Yameen, B., Choi, W. I., Vilos, C., Swami, A., Shi, J., & Farokhzad, O. C. (2014). Insight into nanoparticle cellular uptake and intracellular targeting. Journal of Controlled Release, 190, 485–499.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Lansman, J. B., Hess, P., & Tsien, R. W. (1986). Blockade of current through single calcium channels by Cd2+, Mg2+, and Ca2+. Voltage and concentration dependence of calcium entry into the pore. The Journal of General Physiology, 88(3), 321–347.

    CAS  PubMed  Google Scholar 

  132. Monteilh-Zoller, M. K., Hermosura, M. C., Nadler, M. J., Scharenberg, A. M., Penner, R., & Fleig, A. (2003). TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions. The Journal of General Physiology, 121(1), 49–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. White, R. E., & Hartzell, H. C. (1989). Magnesium ions in cardiac function: regulator of ion channels and second messengers. Biochemical Pharmacology, 38(6), 859–867.

    CAS  PubMed  Google Scholar 

  134. Simon, H.-U., Haj-Yehia, A., & Levi-Schaffer, F. (2000). Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis, 5(5), 415–418.

    CAS  PubMed  Google Scholar 

  135. Premanathan, M., Karthikeyan, K., Jeyasubramanian, K., & Manivannan, G. (2011). Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomedicine: Nanotechnology, Biology and Medicine, 7(2), 184–192.

    CAS  Google Scholar 

  136. Oh, N., & Park, J.-H. (2014). Endocytosis and exocytosis of nanoparticles in mammalian cells. International Journal of Nanomedicine, 9(Suppl 1), 51.

    PubMed  PubMed Central  Google Scholar 

  137. Zhao, F., Zhao, Y., Liu, Y., Chang, X., Chen, C., & Zhao, Y. (2011). Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small, 7(10), 1322–1337.

    CAS  PubMed  Google Scholar 

  138. Xia, T., Kovochich, M., Liong, M., Mädler, L., Gilbert, B., Shi, H., Yeh, J. I., Zink, J. I., & Nel, A. E. (2008). Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano, 2(10), 2121–2134.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Chinni, S. R., & Shisheva, A. (1999). Arrest of endosome acidification by bafilomycin A1 mimics insulin action on GLUT4 translocation in 3T3-L1 adipocytes. Biochemical Journal, 339(3), 599–606.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge Curtin University, Malaysia, for its financial support through the Curtin Sarawak Postgraduate Research Scholarship (CSPRS) scheme, and Life Teck Research Centre, Chennai, India for their support in cell line studies.

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, Faculty of Engineering and Science, Curtin University, CDT 250, 98009, Miri, Sarawak, Malaysia

    Jaison Jeevanandam & Yen San Chan

  2. Chemical Engineering Department, University of Tennessee, Chattanooga, TN, 37403, USA

    Michael K. Danquah

  3. Department of Mechanical Engineering, Faculty of Engineering and Science, Curtin University, CDT 250, 98009, Miri, Sarawak, Malaysia

    Ming Chiat Law

Authors
  1. Jaison Jeevanandam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yen San Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael K. Danquah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming Chiat Law
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Jaison Jeevanandam performed the experiments, Dr. Jaison and Dr. Yen San Chan drafted the manuscript, Prof. Michael Danquah contributed with mechanisms, and Dr. Ming Chiat Law and Prof. Michael Danquah assisted in improving the quality of the manuscript. All authors have reviewed the manuscript.

Corresponding author

Correspondence to Yen San Chan.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOC 1560 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jeevanandam, J., Chan, Y.S., Danquah, M.K. et al. Cytotoxicity Analysis of Morphologically Different Sol-Gel-Synthesized MgO Nanoparticles and Their In Vitro Insulin Resistance Reversal Ability in Adipose cells. Appl Biochem Biotechnol 190, 1385–1410 (2020). https://doi.org/10.1007/s12010-019-03166-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-019-03166-z

Keywords

Search

Navigation