Biological Trace Element Research

, Volume 175, Issue 1, pp 146–155 | Cite as

Functional Improvement in Rats’ Pancreatic Islets Using Magnesium Oxide Nanoparticles Through Antiapoptotic and Antioxidant Pathways

  • Shermineh Moeini-Nodeh
  • Mahban Rahimifard
  • Maryam Baeeri
  • Mohammad AbdollahiEmail author


According to undiscovered toxicity and safety of magnesium oxide nanoparticles (MgO NPs) in isolated pancreatic islet cells, this study was designed to examine the effects of its various concentrations on a time-course basis on the oxidative stress, viability, and function of isolated islets of rat’s pancreas. Pancreatic islets were isolated and exposed to different MgO NP (<100 nm) concentrations within three different time points. After that, oxidative stress biomarkers were investigated and the best exposure time was selected. Then, safety of MgO NPs was investigated by flow cytometry and fluorescent staining, and levels of insulin secretion and caspase activity were measured. The results illustrated a considerable decrease in oxidative stress markers such as reactive oxygen species (ROS) and lipid peroxidation (LPO) levels of pancreatic islets which were treated by MgO NPs for 24 h. Also, in that time of exposure, cell apoptosis investigation by flow cytometry and insulin test showed that MgO NPs, in a concentration of 100 μg/ml, decreased the rate of apoptotic cells via inhibiting caspase-9 activity and made a significant increase in the level of insulin secretion. Data of function and apoptosis biomarkers correlated with each other. It is concluded that the use of MgO NPs in concentration of as low as 100 μg/ml can induce antiapoptotic, antioxidative, and antidiabetic effects in rat pancreatic islets, which support its possible benefit in islet transplantation procedures.


Isolated rat pancreatic islets Magnesium oxide nanoparticles Oxidative stress Toxicology 



Acridine orange


Bovine serum albumin


2′,7′-Dichlorodihydrofluorescein diacetate


Ethidium bromide


Ferric reducing antioxidant power


Lipid peroxidation


Magnesium oxide nanoparticle


3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide




Reactive oxygen species


Total antioxidant power


Thiobarbituric acid


Transmission electron microscope




Ultraviolet visible



The authors thank the Pharmaceutical Sciences Research Center of TUMS for the partial support of this study (Grant No.: 94-01-45-28957). The assistance of Iran National Science Foundation (INSF) is appreciated.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Mody VV, Siwale R, Singh A, Mody HR (2010) Introduction to metallic nanoparticles. Int J Pharm Bio Sci 2(4):282–289Google Scholar
  2. 2.
    Shoae-Hagh P, Rahimifard M, Navaei-Nigjeh M, Baeeri M, Gholami M, Mohammadirad A, et al. (2014) Zinc oxide nanoparticles reduce apoptosis and oxidative stress values in isolated rat pancreatic islets. Biol Trace Elem Res 162(1–3):262–269CrossRefPubMedGoogle Scholar
  3. 3.
    Rahimifard M, Navaei-Nigjeh M, Mahroui N, Mirzaei S, Siahpoosh Z, Nili-Ahmadabadi A, et al. (2014) Improvement in the function of isolated rat pancreatic islets through reduction of oxidative stress using traditional Iranian medicine. Cell J 16(2):147–163PubMedPubMedCentralGoogle Scholar
  4. 4.
    Hosseini A, Baeeri M, Rahimifard M, Navaei-Nigjeh M, Mohammadirad A, Pourkhalili N, et al. (2013) Antiapoptotic effects of cerium oxide and yttrium oxide nanoparticles in isolated rat pancreatic islets. Hum Exp Toxicol 32(5):544–553CrossRefPubMedGoogle Scholar
  5. 5.
    Kiranmai G, Reddy AR (2013) Antioxidant status in MgO nanoparticle-exposed rats. Toxicol Ind Health 29(10):897–903CrossRefPubMedGoogle Scholar
  6. 6.
    Jahangiri L, Kesmati M, Najafzadeh H (2013) Evaluation of analgesic and anti-inflammatory effect of nanoparticles of magnesium oxide in mice with and without ketamine. Eur Rev Med Pharmacol Sci 17(20):2706–2710PubMedGoogle Scholar
  7. 7.
    Patel MK, Md Z, Rizvi Moshahid Alam M, Agrawal VV, Ansari ZA, Malhotra BD, et al. (2013) Antibacterial and cytotoxic effect of magnesium oxide nanoparticles on bacterial and human cells. J Nanoeng Nanomanuf 3(2):162–166CrossRefGoogle Scholar
  8. 8.
    Kumaran RS, Choi YK, Singh V, Song HJ, Song KG, Kim KJ, et al. (2015) In vitro cytotoxic evaluation of MgO nanoparticles and their effect on the expression of ROS genes. Int J Mol Sci 16(4):7551–7564CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Carranza K, Veron D, Cercado A, Bautista N, Pozo W, Tufro A, et al. (2015) Cellular and molecular aspects of diabetic nephropathy and the role of VEGF-A. Nefrologia 35(2):131–138CrossRefPubMedGoogle Scholar
  10. 10.
    Mohseni Salehi Monfared SS, Larijani B, Abdollahi M (2009) Islet transplantation and antioxidant management: a comprehensive review. World J Gastroenterol 15(10):1153–1161CrossRefPubMedGoogle Scholar
  11. 11.
    Kanter M, Coskun O, Korkmaz A, Oter S (2004) Effects of Nigella sativa on oxidative stress and beta-cell damage in streptozotocin-induced diabetic rats. Anat Rec A: Discov Mol Cell Evol Biol 279(1):685–691CrossRefGoogle Scholar
  12. 12.
    Gilbert K, Godbout R, Rousseau G (2016) Caspase-3 activity in the rat amygdala measured by spectrofluorometry after myocardial infarction. J Vis Exp 107:e53207Google Scholar
  13. 13.
    Astaneie F, Afshari M, Mojtahedi A, Mostafalou S, Zamani MJ, Larijani B, et al. (2005) Total antioxidant capacity and levels of epidermal growth factor and nitric oxide in blood and saliva of insulin-dependent diabetic patients. Arch Med Res 36(4):376–381CrossRefPubMedGoogle Scholar
  14. 14.
    Jowzi N, Rahimifard M, Navaei-Nigjeh M, Baeeri M, Darvishi B, et al. (2016) Reduction of chlorpyrifos-induced toxicity in human lymphocytes by selected phosphodiesterase inhibitors. Pestic Biochem Physiol 28:57–62CrossRefGoogle Scholar
  15. 15.
    Rahimifard M, Navaei-Nigjeh M, Baeeri M, Maqbool F, Abdollahi M (2015) Multiple protective mechanisms of alpha-lipoic acid in oxidation, apoptosis and inflammation against hydrogen peroxide induced toxicity in human lymphocytes. Mol Cell Biochem 403(1–2):179–186CrossRefPubMedGoogle Scholar
  16. 16.
    Attari F, Sepehri H, Delphi L, Goliaei B (2009) Apoptotic and necrotic effects of pectic acid on rat pituitary GH3/B6 tumor cells. Iran Biomed J 13(4):229–236PubMedGoogle Scholar
  17. 17.
    Ramkumar KM, Sekar TV, Bhakkiyalakshmi E, Foygel K, Rajaguru P, Berger F, et al. (2013) The impact of oxidative stress on islet transplantation and monitoring the graft survival by non-invasive imaging. Curr Med Chem 20(9):1127–1146CrossRefPubMedGoogle Scholar
  18. 18.
    Karlsson HL, Gustafsson J, Cronholm P, Möller L (2009) Size-dependent toxicity of metal oxide particles—a comparison between nano- and micrometer size. Toxicol Lett 188(2):112–118CrossRefPubMedGoogle Scholar
  19. 19.
    Arora S, Rajwade JM, Paknikar KM (2012) Nanotoxicology and in vitro studies: the need of the hour. Toxicol Appl Pharmacol 258(2):151–165CrossRefPubMedGoogle Scholar
  20. 20.
    Chalkidou A, Simeonidis K, Angelakeris M, Samaras T, Martinez C, Boubeta, et al. (2011) In vitro application of Fe/MgO nanoparticles as magnetically mediated hyperthermia agents for cancer treatment. J Magn Magn Mater 323(6):775–780CrossRefGoogle Scholar
  21. 21.
    Fukui H, Horie M, Endoh S, Kato H, Fujita K, Nishio K, et al. (2012) Association of zinc ion release and oxidative stress induced by intratracheal instillation of ZnO nanoparticles to rat lung. Chem Biol Interact 198(1):29–37CrossRefPubMedGoogle Scholar
  22. 22.
    Jo DH, Kim JH, Lee TG, Kim JH (2015) Size, surface charge, and shape determine therapeutic effects of nanoparticles on brain and retinal diseases. Nanomedicine 11(7):1603–1611PubMedGoogle Scholar
  23. 23.
    Heydary V, Navaei-Nigjeh M, Rahimifard M, Mohammadirad A, et al. (2015) Biochemical and molecular evidences on the protection by magnesium oxide nanoparticles of chlorpyrifos-induced apoptosis in human lymphocytes. J Res Med Sci 20:1021–1031CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hans CP, Chaudhary DP, Bansal DD (2002) Magnesium deficiency increases oxidative stress in rats. Indian J Exp Biol 40(11):1275–1279PubMedGoogle Scholar
  25. 25.
    Buha A, Bulat Z, Dukić-Ćosić D, Matović V (2012) Effects of oral and intraperitoneal magnesium treatment against cadmium-induced oxidative stress in plasma of rats. Arh Hig Rada Toksikol 63(3):247–254CrossRefPubMedGoogle Scholar
  26. 26.
    Süzer T, Coskun E, Islekel H, Tahta K (1999) Neuroprotective effect of magnesium on lipid peroxidation and axonal function after experimental spinal cord injury. Spinal Cord 37(7):480–484CrossRefPubMedGoogle Scholar
  27. 27.
    Ge S, Wang G, Shen Y, Zhang Q, Jia D, Wang H, et al. (2001) Cytotoxic effects of MgO nanoparticles on human umbilical vein endothelial cells in vitro. IET Nanotechnol 5(2):36CrossRefGoogle Scholar
  28. 28.
    Würstle ML, Laussmann MA, Rehm M (2012) The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome. Exp Cell Res 318(11):1213–1220CrossRefPubMedGoogle Scholar
  29. 29.
    Zhou H, Ma Y, Zhou Y, Liu Z, et al. (2003) Effects of magnesium sulfate on neuron apoptosis and expression of caspase-3, bax and bcl-2 after cerebral ischemia-reperfusion injury. Chin Med J 116:1532–1534PubMedGoogle Scholar
  30. 30.
    Kaufmann SH, Hengartner MO (2011) Programmed cell death: alive and well in the new millennium. Trends Cell Biol 11:526–534CrossRefGoogle Scholar
  31. 31.
    Graciano MF, Valle MM, Kowluru A, Curi R, Carpinelli AR (2001) Regulation of insulin secretion and reactive oxygen species production by free fatty acids in pancreatic islets. Islets 3(5):213–223CrossRefGoogle Scholar
  32. 32.
    Alkaladi A, Abdelazim AM, Afifi M (2014) Antidiabetic activity of zinc oxide and silver nanoparticles on streptozotocin-induced diabetic rats. Int J Mol Sci 15(2):2015–2023CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shermineh Moeini-Nodeh
    • 1
  • Mahban Rahimifard
    • 1
  • Maryam Baeeri
    • 1
  • Mohammad Abdollahi
    • 1
    • 2
    • 3
    Email author
  1. 1.Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran
  2. 2.Department of Toxicology and Pharmacology, Faculty of PharmacyTehran University of Medical ScienceTehranIran
  3. 3.Endocrinology and Metabolism Research Center, Institute of Clinical Endocrine SciencesTehran University of Medical SciencesTehranIran

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