Abstract
Parkinson’s disease (PD) is one of the most aggressive neurodegenerative diseases and characterized by the loss of dopamine-sensitive neurons in the substantia nigra region of the brain. There is no any definitive treatment to completely cure PD and existing treatments can only ease the symptoms of the disease. Boron nitride nanoparticles have been extensively studied in nano-biological studies and researches showed that it can be a promising candidate for PD treatment with its biologically active unique properties. In the present study, it was aimed to investigate ameliorative effects of hexagonal boron nitride nanoparticles (hBNs) against toxicity of 1-methyl-4-phenylpyridinium (MPP+) in experimental PD model. Experimental PD model was constituted by application of MPP+ to differentiated pluripotent human embryonal carcinoma cell (Ntera-2, NT-2) culture in wide range of concentrations (0.62 to 2 mM). Neuroprotective activity of hBNs against MPP+ toxicity was determined by cell viability assays including MTT and LDH release. Oxidative alterations by hBNs application in PD cell culture model were investigated using total antioxidant capacity (TAC) and total oxidant status (TOS) tests. The impacts of hBNs and MPP+ on nuclear integrity were analyzed by Hoechst 33258 fluorescent staining method. Acetylcholinesterase (AChE) enzyme activities were determined by a colorimetric assay towards to hBNs treatment. Cell death mechanisms caused by hBNs and MPP+ exposure was investigated by flow cytometry analysis. Experimental results showed that application of hBNs increased cell viability in PD model against MPP+ application. TAS and TOS analysis were determined that antioxidant capacity elevated after hBNs applications while oxidant levels were reduced. Furthermore, flow cytometric analysis executed that MPP+ induced apoptosis was prevented significantly (p < 0.05) after application with hBNs. In a conclusion, the obtained results indicated that hBNs have a huge potential against MPP+ toxicity and can be used in PD treatment as novel neuroprotective agent and drug delivery system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alak G, Parlak V, Aslan ME, et al (2018) Borax Supplementation Alleviates Hematotoxicity and DNA Damage in Rainbow Trout (Oncorhynchus mykiss) Exposed to Copper. Biol Trace Elem Res 1–7. https://doi.org/10.1007/s12011-018-1399-6
Andrews PW (1984) Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell line in vitro. Dev Biol 103:285–293. https://doi.org/10.1016/0012-1606(84)90316-6
Andrews PW, Damjanov I, Simon D, Banting GS, Carlin C, Dracopoli NC, Føgh J (1984) Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro. Lab Investig J Tech Methods Pathol
Andrews PW, Nudelman E, Hakomori S-I, Fenderson BA (1990) Different patterns of glycolipid antigens are expressed following differentiation of TERA-2 human embryonal carcinoma cells induced by retinoic acid, hexamethylene bisacetamide (HMBA) or bromodeoxyuridine (BUdR). Differentiation 43:131–138. https://doi.org/10.1111/j.1432-0436.1990.tb00439.x
Beal, M.F., 2001. Experimental models of Parkinson’s disease., Nature Reviews Neuroscience. https://doi.org/10.1038/35072550
Chen X, Wu P, Rousseas M et al (2009) Boron nitride nanotubes are noncytotoxic and can be functionalized for interaction with proteins and cells. J Am Chem Soc. https://doi.org/10.1021/ja807334b
Chung KKK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM (2001) Parkin ubiquitinates the α-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. https://doi.org/10.1038/nm1001-1144
Ciofani G, Danti S, Genchi GG, D'Alessandro D, Pellequer JL, Odorico M, Mattoli V, Giorgi M (2012) Pilot in vivo toxicological investigation of boron nitride nanotubes. Int J Nanomedicine 7:19–24
Emsen B, Aslan A, Togar B, Turkez H (2016) In vitro antitumor activities of the lichen compounds olivetoric, physodic and psoromic acid in rat neuron and glioblastoma cells. Pharm Biol 54:1748–1762. https://doi.org/10.3109/13880209.2015.1126620
Emsen B, Aslan A, Turkez H, et al (2018a) The anti-cancer efficacies of diffractaic, lobaric, and usnic acid: In vitro inhibition of glioma. J Cancer Res Ther 14:941. https://doi.org/10.4103/0973-1482.177218
Emsen B, Togar B, Turkez H, Aslan A (2018b) Effects of two lichen acids isolated from Pseudevernia furfuracea (L.) Zopf in cultured human lymphocytes. Zeitschrift fur Naturforsch - Sect C J Biosci. https://doi.org/10.1515/znc-2017-0209
Esteves M, Cristóvão AC, Saraiva T, Rocha SM, Baltazar G, Ferreira L, Bernardino L (2015) Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for Parkinson’s disease. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2015.00020
Esteves ARF, Domingues AF, Ferreira IL et al (2008) Mitochondrial function in Parkinson’s disease cybrids containing an nt2 neuron-like nuclear background. Mitochondrion. https://doi.org/10.1016/j.mito.2008.03.004
Gerretsen FC, de Hoop H (1954) Boron, an essential micro-element for Azotobacter chroococcum. Plant Soil 5:349–367. https://doi.org/10.1007/BF01354457
Haas ARC (2002) Boron as an essential element for healthy growth of citrus. Bot Gaz. https://doi.org/10.1086/334073
Herrero M, Ibáñez E, Cifuentes A (2005) Analysis of natural antioxidants by capillary electromigration methods. J Sep Sci 28:883–897. https://doi.org/10.1002/jssc.200400104
Janhom P, Dharmasaroja P (2015) Neuroprotective effects of alpha-mangostin on MPP+-induced apoptotic cell death in neuroblastoma SH-SY5Y cells. J Toxicol. https://doi.org/10.1155/2015/919058
Jankovic J, Kapadia AS (2001) Functional decline in Parkinson disease. Arch Neurol. https://doi.org/10.1001/archneur.58.10.1611
Jedrzejczak-Silicka M, Trukawka M, Dudziak M, Piotrowska K, Mijowska E (2018) Hexagonal boron nitride functionalized with au nanoparticles—properties and potential biological applications. Nanomaterials. https://doi.org/10.3390/nano8080605
Jones-Villeneuve EM, Rudnicki MA, Harris JF, McBurney MW (1983) Retinoic acid-induced neural differentiation of embryonal carcinoma cells. Mol Cell Biol. https://doi.org/10.1128/mcb.3.12.2271
Kawasaki H, Taira K (2012) Functional analysis of microRNAs during the retinoic acid-induced neuronal differentiation of human NT2 cells. Nucleic Acids Symp Ser. https://doi.org/10.1093/nass/3.1.243
Kim GH, Kim JE, Rhie SJ, Yoon S (2015) The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol. https://doi.org/10.5607/en.2015.24.4.325
Kıvanç M, Barutca B, Koparal AT, Göncü Y, Bostancı SH, Ay N (2018) Effects of hexagonal boron nitride nanoparticles on antimicrobial and antibiofilm activities, cell viability. Mater Sci Eng C. https://doi.org/10.1016/j.msec.2018.05.028
Korsaks V (2015) Hexagonal boron nitride luminescence dependent on vacuum level and surrounding gases. Mater Res Bull. https://doi.org/10.1016/j.materresbull.2015.06.032
Langston JW, Langston EB, Irwin I (1984) MPTP-induced parkinsonism in human and non-human primates--clinical and experimental aspects. Acta Neurol Scand Suppl 100:49–54
Lee VMY, Andrews PW (1986) Differentiation of NTERA-2 clonal human embryonal carcinoma cells into neurons involves the induction of all three neurofilament proteins. J Neurosci. https://doi.org/10.1523/jneurosci.06-02-00514.1986
Lee DH, Kim CS, Lee YJ (2011) Astaxanthin protects against MPTP/MPP+-induced mitochondrial dysfunction and ROS production in vivo and in vitro. Food Chem Toxicol. https://doi.org/10.1016/j.fct.2010.10.029
Marinelli L, Fornasari E, Di Stefano A, et al (2017) (R)-α-Lipoyl-Gly-L-Pro-L-Glu dimethyl ester as dual acting agent for the treatment of Alzheimer’s disease. Neuropeptides 66:52–58. https://doi.org/10.1016/j.npep.2017.09.001
Marzinke MA, Henderson EM, Yang KS, See AWM, Knutson DC, Clagett-Dame M (2010) Calmin expression in embryos and the adult brain, and its regulation by all-trans retinoic acid. Dev Dyn Off Publ Am Assoc Anatomists. https://doi.org/10.1002/dvdy.22171
Merlo A, Mokkapati VRSS, Pandit S, Mijakovic I (2018) Boron nitride nanomaterials: biocompatibility and bio-applications. Biomater Sci 6:2298–2311. https://doi.org/10.1039/C8BM00516H
Mooney JB, Radding SB (2003) Spray pyrolysis processing. Annu Rev Mater Sci. https://doi.org/10.1146/annurev.ms.12.080182.000501
Mori Y, Matsui T, Omote D, Fukuda M (2013) Small GTPase Rab39A interacts with UACA and regulates the retinoic acid-induced neurite morphology of Neuro2A cells. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2013.04.051
Niedzielska E, Smaga I, Gawlik M, Moniczewski A, Stankowicz P, Pera J, Filip M (2016) Oxidative stress in neurodegenerative diseases. Mol Neurobiol. https://doi.org/10.1007/s12035-015-9337-5
Patterson AL (1939) The scherrer formula for X-ray particle size determination. Phys Rev. https://doi.org/10.1103/PhysRev.56.978
Pleasure SJ, Lee VM (1993) NTera 2 cells: a human cell line which displays characteristics expected of a human committed neuronal progenitor cell. J Neurosci Res 35:585–602. https://doi.org/10.1002/jnr.490350603
Sanders LH, Timothy Greenamyre J (2013) Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radic Biol Med 62:111–120. https://doi.org/10.1016/j.freeradbiomed.2013.01.003
Schlachetzki JCM, Saliba SW, de Oliveira ACP (2013) Studying neurodegenerative diseases in culture models. Rev Bras Psiquiatr. https://doi.org/10.1590/1516-4446-2013-1159
Schwartz CM, Spivak CE, Baker SC et al (2005) NTera2: a model system to study dopaminergic differentiation of human embryonic stem cells. Stem Cells Dev. https://doi.org/10.1089/scd.2005.14.517
Sheehan JP, Palmer PE, Helm GA, Tuttle JB (1997) MPP+ induced apoptotic cell death in SH-SY5Y neuroblastoma cells: an electron microscope study. J Neurosci Res. https://doi.org/10.1002/(SICI)1097-4547(19970501)48:3<226::AID-JNR5>3.0.CO;2-H
Shimizu S, Kondo M, Miyamoto Y, Hayashi M (2002) Foxa (HNF3) up-regulates vitronectin expression during retinoic acid-induced differentiation in mouse neuroblastoma Neuro2a cells. Cell Struct Funct. https://doi.org/10.1247/csf.27.181
Shimohama S, Sawada H, Kitamura Y, Taniguchi T (2003) Disease model: Parkinson’s disease. Trends Mol Med. https://doi.org/10.1016/S1471-4914(03)00117-5
Singer TP, Castagnoli N, Ramsay RR, Trevor AJ (1987) Biochemical events in the development of parkinsonism induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine. J Neurochem. https://doi.org/10.1111/j.1471-4159.1987.tb03384.x
Stefanis L, Burke RE, Greene LA (1997) Apoptosis in neurodegenerative disorders. Curr Opin Neurol 10:299–305. https://doi.org/10.1097/00019052-199708000-00004
Subramaniam SR, Chesselet M-F (2013) Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol 106–107:17–32. https://doi.org/10.1016/j.pneurobio.2013.04.004
Sugahara M, Nakaoki Y, Yamaguchi A, Hashimoto K, Miyamoto Y (2019) Vitronectin is involved in the morphological transition of Neurites in retinoic acid-induced neurogenesis of neuroblastoma cell line Neuro2a. Neurochem Res 44:1621–1635. https://doi.org/10.1007/s11064-019-02787-4
Turkez H (2008) Effects of boric acid and borax on titanium dioxide genotoxicity. J Appl Toxicol 28:658–664. https://doi.org/10.1002/jat.1318
Türkez H, Arslan ME, Sönmez E, Açikyildiz M, Tatar A, Geyikoğlu F (2019a) Synthesis, characterization and cytotoxicity of boron nitride nanoparticles: emphasis on toxicogenomics. Cytotechnology. 71:351–361. https://doi.org/10.1007/s10616-019-00292-8
Türkez H, Arslan ME, Sönmez E, et al (2019) Synthesis, characterization and cytotoxicity of boron nitride nanoparticles: emphasis on toxicogenomics. Cytotechnology. https://doi.org/10.1007/s10616-019-00292-8
Turkez H, Geyikoglu F (2010) Boric acid: a potential chemoprotective agent against aflatoxin b1toxicity in human blood. Cytotechnology. https://doi.org/10.1007/s10616-010-9272-2
Turkez H, Geyikoglu F, Tatar A, et al (2012) The effects of some boron compounds against heavy metal toxicity in human blood. Exp Toxicol Pathol 64:93–101. https://doi.org/10.1016/j.etp.2010.06.011
Turkez H, Tatar A, Hacimuftuoglu A, Ozdemir E (2010c) Boric acid as a protector against paclitaxel genotoxicity. Acta Biochim Pol. 57:95–97 https://doi.org/10.18388/abp.2010_2378
Üstündaǧ A, Behm C, Föllmann W et al (2014) Protective effect of boric acid on lead- and cadmium-induced genotoxicity in V79 cells. Arch Toxicol 88:1281–1289. https://doi.org/10.1007/s00204-014-1235-5
Zang LY, Misra HP (1993) Acetylcholinesterase inhibition by 1-methyl-4-phenylpyridinium ion, a bioactivated metabolite of MPTP. Mol Cell Biochem 126:93–100. https://doi.org/10.1007/BF00925686
Zeller M, Strauss WL (1995) Retinoic acid induces cholinergic differentiation of NTera 2 human embryonal carcinoma cells. Int J Dev Neurosci. https://doi.org/10.1016/0736-5748(95)00025-C
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Küçükdoğru, R., Türkez, H., Arslan, M.E. et al. Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis. Metab Brain Dis 35, 947–957 (2020). https://doi.org/10.1007/s11011-020-00559-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-020-00559-6