Nanomedicine Research Journal

Nanomedicine Research Journal

Calcium current block enhances the toxicity of CuO nanoparticles to motor and nuclear units of an in vivo single-cell model exposed to a static magnetic field

Document Type : Original Research Article

Authors
1 MSc student, Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran
2 Associate Prof., Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran
3 Neurophysiology Research Center of Shahed University, Tehran, Iran
4 Associate Prof., Department of Physics, Faculty of Basic Sciences, Shahed University, Tehran, Iran
Abstract
Objective(s): MgSO4, a calcium (Ca) channel blocker, can disrupt ionic homeostasis. However, its effect on the synergy of nanomaterials in static magnetic fields (SMF) with therapeutic use has not been investigated in an in vivo model. We used the blocker alone and with CuO nanoparticles (NPs) to investigate the synergy of SMF and NPs in living P. caudatum.
Methods: The experimental model was grown in straw and purified after serial cultivation. The pure environment was then divided into two groups. One group was exposed to SMF (0.061 mT) for 72 hours and the second group was exposed to natural, geostatic laboratory conditions. A sample of each group (0.1 mL) was treated with MgSO4 or/and CuO NPs (1, 3, 9 μg/μL) under a fixed objective lens (4x) for 25 times in 30 seconds with 5-second time interval. The control group received only 1 μL of distilled water. Sigmoid and avoidance movements of paramecia were counted. Trichocyst, macronucleus, pellicle, Ca channel and nitric oxide synthase (NOS) activation were studied. All data were analysed using ANOVA (α = 0.05).
Results: No changes in Ca channel density or NOS activation were observed due to exposure of paramecia to MgSO4 alone. However, the movement of paramecia using MgSO4 with high doses of CuO NPs under SMF was reduced, and the pellicular and macronuclear units were destroyed, indicating increased toxicity of CuO NPs. 
Conclusions: MgSO4 can affect the diamagnetic state of CuO NPs under SMF, thereby intensifying the non-protective effects of nanomaterials.
Keywords

Subjects


1.    Ali A, et al. Review on recent progress in magnetic nanoparticles: synthesis, characterization, and diverse applications. Front Chem. 2021;9:629054. https://doi.org/10.3389/fchem.2021.629054
2.    Elahee KB, Poinapen D. Effects of static magnetic fields on growth of Paramecium caudatum. Bioelectromagnetics. 2006;27:26-34. https://doi.org/10.1002/bem.20172 
3.    Faraji M, Fadavi Q. Application of magnetic nanoparticles in food science and technology. Iran J Nutr Sci Food Technol. 2013;8:239-52. 
4.    Tan B, et al. Toxic effects of copper nanoparticles on Paramecium bursaria-Chlorella symbiotic system. Front Microbiol. 2022;13:834208. https://doi.org/10.3389/fmicb.2022.834208 
5.    Kim KS, et al. Reactive oxygen species-activated nanomaterials as theranostic agents. Nanomedicine (Lond). 2015;10:2709-23. https://doi.org/10.2217/nnm.15.108 
6.    Benguigui M, et al. Copper oxide nanoparticles inhibit pancreatic tumor growth primarily by targeting tumor initiating cells. Sci Rep. 2019;9:12613. https://doi.org/10.1038/s41598-019-48959-8 
7.    Hsu CY, et al. An overview of nanoparticles in drug delivery: Properties and applications. S Afr J Chem Eng. 2023;46:233-70. https://doi.org/10.1016/j.sajce.2023.08.009 
8.    Aishajiang R, et al. Recent advances in cancer therapeutic copper-based nanomaterials for antitumor therapy. Molecules. 2023;28:2303. https://doi.org/10.3390/molecules28052303 
9.    Cheng X, Xie Q, Sun Y. Advances in nanomaterial-based targeted drug delivery systems. Front Bioeng Biotechnol. 2023;11:1177151. https://doi.org/10.3389/fbioe.2023.1177151 
10.    Egbuna C, et al. Toxicity of nanoparticles in biomedical application. J Toxicol. 2021;2021:9954443. https://doi.org/10.1155/2021/9954443 
11.    Wróblewska A, et al. Macrophages as promising carriers for nanoparticle delivery in anticancer therapy. Int J Nanomedicine. 2023;18:4521-39. https://doi.org/10.2147/IJN.S421173 
12.    Sheikhmohammadi M, Karami M, Hajnorouzi A. Effectiveness of Fe2O3 nanoparticles more than magnetic field against the destructive effect of colchicine on Paramecium caudatum. J Basic Clin Pathophysiol. 2022;10:30-7. 
13.    Chang YN, et al. The Toxic Effects and Mechanisms of CuO and ZnO Nanoparticles. Materials. 2012;5:5122850. https://doi.org/10.3390/ma5122850 
14.    Devaraji M, Thanikachalam PV, Elumalai K. The potential of copper oxide nanoparticles in nanomedicine: A comprehensive review. Biotechnol Notes. 2024;5:80-99. https://doi.org/10.1016/j.biotno.2024.06.001 
15.    Davoudi-Farimani S, et al. The effect of copper oxide nanoparticles on the expression of the USP9Y gene in rat testicles. Feyz Med Sci J. 2018;22:120-7. 
16.    Yahyaei B, Sabbagh M. Investigation of accumulation and tissue effects due to injection of biologically produced magnetic iron nanoparticles in renal tissue of rats in response to electromagnetic field by histopathological and ICP methods. Yafte. 2021;23:304-18. 
17.    Nomoev AV, et al. Structure and mechanism of the formation of core-shell nanoparticles obtained through a one-step gas-phase synthesis by electron beam evaporation. Beilstein J Nanotechnol. 2015;6:874-80. https://doi.org/10.3762/bjnano.6.89 
18.    Shahrokhi SS, Karami M, Kazemi B. Effect of temperature and organic & inorganic factors on growth and proliferation of Paramecium caudatum. Cell Mol Res (Iran J Biol). 2013;26:200-7. 
19.    Brette R. Integrative neuroscience of Paramecium, a “Swimming Neuron”. eNeuro. 2021;8(3): ENEURO .0018-21.2021. https://doi.org/10.1523/ENEURO .0018-21.2021 
20.    Karami M, Moezzi SS, Kazemi B, Shahrokhi SS. Paramecium caudatum Avoids from Naloxone. Am J Infect Dis Microbiol. 2013;1:21-5. https://doi.org/10.12691/ajidm-1-1-4 
21.    Shahrokhi SS, Karami M, Kazemi B. Response to Morphine in a unicellular animal model (Paramecium caudatum). Physiol Pharmacol. 2011;15:318-29. 
22.    Habbache N, et al. Leaching of copper oxide with different acid solutions. Chem Eng J. 2009;152:503-8. https://doi.org/10.1016/j.cej.2009.05.020 
23.    Hajnorouzi A. Two ultrasonic applications for the synthesis of nanostructured copper oxide (II). Ultrason Sonochem. 2020;64:105020. https://doi.org/10.1016/j.ultsonch.2020.105020 
24.    Wood DC. Protozoa as models of stimulus transduction. In: Aneural Organisms in Neurobiology. Eisenstein EM, editor. New York: Plenum Press; 1975. p. 5-23. (Advances in Behavioral Biology; vol 13). https://doi.org/10.1007/978-1-4613-4473-5_2 
25.    Lodh S, et al. Voltage-gated calcium channels of Paramecium cilia. J Exp Biol. 2016;219:3028-38. https://doi.org/10.1242/jeb.141234 
26.    Jeftinija DM, et al. The Ca(V) 1.2 Ca(2+) channel is expressed in sarcolemma of type I and IIA myofibers of adult skeletal muscle. Muscle Nerve. 2007;36:482-90. https://doi.org/10.1002/mus.20842 
27.    Jomova K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97:2499-574. https://doi.org/10.1007/s00204-023-03562-9 
28.    Malvin GM, Cecava N, Nelin LD. Nitric oxide production and thermoregulation in Paramecium caudatum. Acta Protozool. 2003;42:259-67. 
29.    Langridge PD, Kay RR. Blebbing of Dictyostelium cells in response to chemoattractant. Exp Cell Res. 2006;312:2009-17. https://doi.org/10.1016/j.yexcr.2006.03.007 
30.    Ladenburger EM, et al. Novel types of Ca2+ release channels participate in the secretory cycle of Paramecium cells. Mol Cell Biol. 2009;29:3605-22. https://doi.org/10.1128/MCB.01592-08 
31.    Kurzay D, et al. Toxic effects of acephate on Paramecium caudatum with special emphasis on morphology, behaviour, and generation time. Pestic Biochem Physiol. 2006;131:86. https://doi.org/10.1016/j.pestbp.2006.02.005 
32.    Xie J, et al. Nanomaterial-based blood-brain-barrier (BBB) crossing strategies. Biomaterials. 2019;224:119491. https://doi.org/10.1016/j.biomaterials.2019.119491 
33.    Xiao J, et al. Autophagy deficiency exacerbates acute lung injury induced by copper oxide nanoparticles. J Nanobiotechnology. 2021;19:162. https://doi.org/10.1186/s12951-021-00909-1 
34.    Farinha P, Coelho JPM, Reis CP. A comprehensive updated review on magnetic nanoparticles in diagnostics. Nanomaterials. 2021;11:3432. https://doi.org/10.3390/nano11123432 
35.    Wu H, et al. Static magnetic fields regulate T-type calcium ion channels and mediate mesenchymal stem cells proliferation. Cells. 2022;11(15):2460. https://doi.org/10.3390/cells11152460