Abstract
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.
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Abbreviations
- AO:
-
Acridine orange
- BSA:
-
Bovine serum albumin
- DCFH-DA:
-
2′,7′-Dichlorodihydrofluorescein diacetate
- EB:
-
Ethidium bromide
- FRAP:
-
Ferric reducing antioxidant power
- LPO:
-
Lipid peroxidation
- MgO NPs:
-
Magnesium oxide nanoparticle
- MTT:
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- NPs:
-
Nanoparticles
- ROS:
-
Reactive oxygen species
- TAP:
-
Total antioxidant power
- TBA:
-
Thiobarbituric acid
- TEM:
-
Transmission electron microscope
- TPTZ:
-
2,4,6-Tripyridyl-s-triazine
- UV-Vis:
-
Ultraviolet visible
References
Mody VV, Siwale R, Singh A, Mody HR (2010) Introduction to metallic nanoparticles. Int J Pharm Bio Sci 2(4):282–289
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):262–269
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):147–163
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):544–553
Kiranmai G, Reddy AR (2013) Antioxidant status in MgO nanoparticle-exposed rats. Toxicol Ind Health 29(10):897–903
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):2706–2710
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):162–166
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):7551–7564
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):131–138
Mohseni Salehi Monfared SS, Larijani B, Abdollahi M (2009) Islet transplantation and antioxidant management: a comprehensive review. World J Gastroenterol 15(10):1153–1161
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):685–691
Gilbert K, Godbout R, Rousseau G (2016) Caspase-3 activity in the rat amygdala measured by spectrofluorometry after myocardial infarction. J Vis Exp 107:e53207
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):376–381
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 28:57–62
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):179–186
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):229–236
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):1127–1146
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):112–118
Arora S, Rajwade JM, Paknikar KM (2012) Nanotoxicology and in vitro studies: the need of the hour. Toxicol Appl Pharmacol 258(2):151–165
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):775–780
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):29–37
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):1603–1611
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 20:1021–1031
Hans CP, Chaudhary DP, Bansal DD (2002) Magnesium deficiency increases oxidative stress in rats. Indian J Exp Biol 40(11):1275–1279
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):247–254
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):480–484
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):36
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):1213–1220
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 116:1532–1534
Kaufmann SH, Hengartner MO (2011) Programmed cell death: alive and well in the new millennium. Trends Cell Biol 11:526–534
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):213–223
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):2015–2023
Acknowledgments
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.
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The authors declare that they have no conflict of interest.
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Shermineh Moeini-Nodeh and Mahban Rahimifard contributed equally to this work.
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Moeini-Nodeh, S., Rahimifard, M., Baeeri, M. et al. Functional Improvement in Rats’ Pancreatic Islets Using Magnesium Oxide Nanoparticles Through Antiapoptotic and Antioxidant Pathways. Biol Trace Elem Res 175, 146–155 (2017). https://doi.org/10.1007/s12011-016-0754-8
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DOI: https://doi.org/10.1007/s12011-016-0754-8