Evaluation of toxic effects of magnetic contrast diagnostic gadolinium-containing nanocomposite

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Introduction. In recent years, magnetic nanoparticles, which can simultaneously have a therapeutic effect on the pathological focus, are used to magnify contrast enhancement and increase diagnostic sensitivity during magnetic resonance therapy (MRT). The last is carried out by the effective capture of neutrons, which among all the chemical elements is most pronounced in gadolinium. The use of gadolinium nanoparticles encapsulated in a polymeric matrix allows increasing the bioavailability of nanoparticles, reduces the possible toxicity of drugs.

Aim. Evaluation of impact of new nanocomposite magnetically active metal complex gadolinium system on the morphofunctional state of the nervous tissue, liver, and kidney of rats.

Material and methods. Experimental studies of biological effects of gadolinium-arabinogalactan nanocomposite (Gd-AG) were carried out on rats that were injected intraperitoneally for 10 days at the dose of 500 μg/kg in 0.5 ml of saline. Animals were sacrificed by decapitation under light ether anesthesia the next day after the end of exposure. To perform pathological studies, frontal sections of the temporal-parietal zone of the sensorimotor cortex, liver and kidney tissues were stained on ordinary histological glass slides with hematoxylin and eosin for viewing microscopic picture. The immunohistochemical method was used to determine the activity of the bcl-2, caspase-3 and hsp70 modulatory protein in apoptosis of white rats in brain neurons and to study the biological response of the organism at the subcellular level.

Results. Histological analysis of tissues revealed a pronounced compensatory response of liver, a violation of the functional activity of kidneys. A decrease in the total number of normal neurons per unit area in brain tissue and an increase in the number of acts of neuronophagy indicate the initial stage of neurodegenerative process. Evaluation of the intracellular metabolism of neurons has not established the presence of signs characteristic of apoptotic process.

Conclusion. The subacute effect of Gd-AG in a dose of 500 µg/kg causes a disturbance of morphofunctional state of liver, kidneys and nervous tissue, as well as modulation of cellular proteomics.

作者简介

Larisa Sosedova

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

编辑信件的主要联系方式.
Email: sosedlar@mail.ru
ORCID iD: 0000-0003-1052-4601

MD, Ph.D., DSci., Professor, Head of Laboratory of biomodeling and translational medicine of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation.

e-mail: sosedlar@mail.ru

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E. Titov

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

Email: noemail@neicon.ru
ORCID iD: 0000-0002-0665-8060
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M. Novikov

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

Email: noemail@neicon.ru
ORCID iD: 0000-0002-6100-6292
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V. Vokina

East-Siberian Institute of Medical and Ecological Research

Email: noemail@neicon.ru
ORCID iD: 0000-0002-8165-8052
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V. Rukavishnikov

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

Email: noemail@neicon.ru
ORCID iD: 0000-0003-2536-1550
俄罗斯联邦

参考

  1. Laurent S., Dutz S., Häfeli U.O., Mahmoudi M. Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. Adv Colloid Interface Sci. 2011; 166: 8-23. https://doi.org/10.1016/j.cis.2011.04.003
  2. Yigit M.V., Moore A., Medarova Z. Magnetic nanoparticles for cancer diagnosis and therapy. Pharm Res. 2012; 29 (5): 1180-8. https://doi.org/10.1007/s11095-012-0679-7
  3. Hilger I., Kaiser W.A. Iron oxide-based nanostructures for MRI and magnetic hyperthermia. Nanomedicine (Lond). 2012; 7 (9): 1443-59. https://doi.org/10.2217/nnm.12.112
  4. Reddy L.H., Arias J.L., Nicolas J., Couvreur P. Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chem Rev. 2012; 112 (11): 5818-78. https://doi.org/10.1021/cr300068p
  5. Akgun H., Gonlusen G., Cartwright J., Suki W.N., Truong L.D. Are gadolinium-based contrast media nephrotoxic? A renal biopsy study. Arch Pathol Lab Med. 2006; 130 (9): 1354-7. https://doi.org/10.1043/1543-2165(2006)130[1354:AGCMNA]2.0.CO;2
  6. Blasco-Perrina H., Glaserb B., Pienkowskic M., Perond J.M., Payen J.L. Gadolinium induced recurrent acute pancreatitis. Pancreatology. 2013; 13 (1): 88-9. https://doi.org/10.1016/j.pan.2012.12.002
  7. Hui F.K., Mullins M. Persistence of gadolinium contrast enhancement in CSF: a possible harbinger of gadolinium neurotoxicity? Am J Neuroradiol. 2009; 30 (1): 1. https://doi.org/10.3174/ajnr.A1205
  8. Lesnichaya M.V., Aleksandrova G.P., Feoktistova L.P., Sapozhnikov A.N., Fadeeva T.V., Sukhov B.G. et al. Silver-containing nanocomposites based on galactomannan and carrageenan: synthesis, structure, and antimicrobial properties. Rossiyskiy khimicheskiy vestnik [Russian Chemical Bulletin]. 2010; 59 (12): 2266-71. https://doi.org/10.1007/s11172-010-0395-6
  9. Kuznetsova N.P., Ermakova T.G., Pozdnyakov A.S., Emel’Yanov A.I., Prozorova G.F. Synthesis and characterization of silver polymer nanocomposites of 1-vinyl-1,2,4-triazole with acrylonitrile. Rossiyskiy khimicheskiy vestnik [Russian chemical bulletin]. 2013; 11: 2509-13.
  10. Jong W.H., Borm P.J. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine. 2008; 3: 133-49.
  11. Sukhov B.G., Pogodaeva N.N., Kuznetsov S.V., Kupriyanovich Y.N., Trofimov B.A., Yurinova et al. Рrebiotic effect of native noncovalent arabinogalactan - flavonoid conjugates on bifidobacteria. Rossiyskiy khimicheskiy vestnik [Russian Chemical Bulletin]. 2014; 9: 2189-94.
  12. Sukhov B.G., Trofimov B.A. Multifunctional nanobiocomposites: synthesis, structure, physicochemical and biological properties. In: XVI International Youth Conference on Luminescence and Laser Physics, dedicated to the 100th anniversary of Irkutsk State University. Theses of lectures and reports. Irkutsk; 2018: 146–7. (in Russian)
  13. Sukhov B.G., Trofimov B.A. The directed synthesis of nanobiocomposites with an unusual complex of magnetic, optical, catalytic and biologically active properties. In: Magnetic materials. New technologies. Proceedinds of the VIII Baikal International Conference. Irkutsk; 2018: 42. (in Russian)
  14. Rukavishnikov V.S., Novikov M.A., Titov E.A., Sosedova L.M., Vokina V.A., Yakimova N.L. Estimation of toxic properties of nanocomposites containing nanoparticles of bismuth, gadolinium, and silver. Тrace Elem Electroly. 2018; 35: 203-6
  15. Rukavishnikov V.S., Sosedova L.M., Vokina V.A., Titov E.A., Novikov M.A., Yakimova N.L. Evaluation of the neurotoxicity of nanometals encapsulated on arabinogalactan matrix. Meditsina truda i promyshlennaya ekologiya [Russian Journal of Occupational Health and Industrial Ecology]. 2017; 10: 25–9. (in Russian)
  16. Sosedova L.M., Novikov M.A., Titov E.A. Features of the expression of apoptosis-regulating proteins in neurons of white rats when exposed to nano-silver, encapsulated in a polymer matrix. Toksikologicheskiy vestnik. 2016; 6: 48–53. (in Russian)
  17. Aime S., Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging. 2009; 30 (6): 1259-67. https://doi.org/10.1002/jmri.21969
  18. Тitov Е.А., Novikov М.А., Sosedova L.М. Еffect of silver nanoparticles encapsulated in a polymer matrix on the structure of nervous tissue and expression of caspase-3. Nanotechnol Russ. 2015; 10 (7-8): 640-4. https://doi.org/10.1134/S1995078015040205
  19. Sosedova L.M., Filippova T.M. The Effects of Nanosilver, Encapsulated in a Polymeric Matrix, on Albino Rats Brain Tissue. Nano Hybrids and Composites. 2017; 13: 263-7. https://doi.org/10.4028/www.scientific.net/NHC.13.263
  20. Kanal E., Tweedle M.F. Residual or retained gadolinium: practical implications for radiologists and our patients. Radiology. 2015; 275: 630-4. https://doi.org/10.1148/radiol.2015150805
  21. Ide J.-M., Port M., Robic C., Medina C., Sabatou M., Corot C. Role of thermodynamic and kinetic parameters in gadolinium chelate. J Magn Reson Imaging. 2009; 30: 1249-58. https://doi.org/10.1002/jmri.21967
  22. Quarles L.D., Hartle J.E., Middleton J.P. Aluminum-induced DNA synthesis in osteoblasts: mediation by a G-protein coupled cation sensing mechanism. J Cell Biochem. 1994; 56 (1): 106-17. https://doi.org/10.1002/jcb.240560115
  23. Pałasz A., Czekaj P. Toxicological and cytophysiological aspects of lanthanides action. Acta Biochim Pol. 2000; 47: 1107-14.
  24. Feng X., Xia Q., Yuan L., Yang X., Wang K. Impaired mitochondrial function and oxidative stress in rat cortical neurons: implications for gadolinium-induced neurotoxicity. Neurotoxicology. 2010; 31: 391-8. https://doi.org/10.1016/j.neuro.2010.04.003
  25. Xia Q., Feng X.D., Huang H.F., Du L.Y., Yang X.D., Wang K. Gadolinium-induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons. J Neurochem. 2011; 117: 38-47. https://doi.org/10.1111/j.1471-4159.2010.07162.x
  26. Heinrich M.C., Kuhlmann M.K., Kohlbacher S., Scheer M., Grgic A., Heckmann M.B. et al. Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular cells at angiographic concentrations: in vitro study. Radiology. 2007; 242:425-34. https://doi.org/10.1148/radiol.2422060245
  27. Rogosnitzky M., Branch S. Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms. BioMetals. 2016; 29 (3): 365-76. https://doi.org/10.1007/s10534-016-9931-7
  28. Chen R., Ling D. Parallel comparative studies on mouse toxicity of oxide nanoparticle-and gadolinium-based T1 MRI contrast agents. ACS Nano. 2015; 9 (12): 12425-35.
  29. Blasco-Perrin H., Glaser B., Pienkowski M., Peron J.M., Payen J.L. Gadolinium induced recurrent acute pancreatitis. Pancreatology. 2013; 13: 88-9. https://doi.org/10.1021/acsnano.5b05783
  30. Ray D.E., Cavanagh J.B., Nolan C.C., Williams S.C.R. Neurotoxic effects of gadopentetate dimeglumine: behavioral disturbance and morphology after intracerebroventricular injection in rats. Am J Neuroradiol. 1996; 17 (2): 365-73.

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版权所有 © Sosedova L.M., Titov E.A., Novikov M.A., Vokina V.A., Rukavishnikov V.S., 2019


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