Effects of selenium oxide nanoparticles on the morphofunctional state of the liver: Experimental data

View or download the full article: 
UDC: 
613.6.02
Authors: 

Yu.V. Ryabova, М.P. Sutunkova, А.I. Chemezov, I.А. Minigalieva, Т.V. Bushueva, I.G. Shelomentsev, S.V. Klinova, R.R. Sakhautdinova

Organization: 

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Yekaterinburg, 620014, Russian Federation

Abstract: 

Copper smelters are the sources of emission of complex aerosols containing, inter alia, selenium-containing nanoparticles (NPs). It is very difficult to adequately estimate the hazard posed by such particles since available data on them are scarce and have been obtained in comparatively few experimental studies with rather contradicting results.

The aim of our study was to determine toxic health effects of selenium-containing nanoparticles more precisely with a focus on liver as a target organ.

Liver toxicity following exposure to suspended selenium oxide nanoparticles was investigated in a sub-chronic experiment on outbred male albino rats. The suspension was prepared by laser ablation of 99%-pure selenium plates. We examined ultrastructural changes by electron microscopy, did cytological and histological analyses of the liver, biochemical blood testing and metabolomic blood screening.

We observed lesions in the liver and inhibited secretory functions at various levels, from molecular to organismic, in the exposed animals. The microscopic examination showed that the number of normal and normal-vesicular mitochondria in liver cells went down by 7.78 %, p < 0.05; the metabolomic screening established lower levels of glycocholic acid in blood serum, р < 0.001; levels of alanine aminotransferase in blood serum grew by 30 %, p < 0.05; the number of acaryotic hepatocytes demonstrated a 3.1-fold increase, p < 0.05, according to the results of histological assessment of liver specimens. The touch smears of the liver examined showed a 2.2-fold increase in the number of degenerated hepatocytes (p < 0.05).

These experimental data can be used to estimate a potential hazard of selenium-containing nanoparticles within social-hygienic monitoring and biomedical predictions of health damage caused by exposure to such NPs. Altered levels of lysophos-phatidylinositol can be a marker of exposure to the examined NPs and necessitate the search for early diagnostic predictors of associated health disorders.

Keywords: 
toxicity, hazard assessment, nanoparticles, selenium, liver, mechanism of action, in vivo, experiment
Ryabova Yu.V., Sutunkova М.P., Chemezov А.I., Minigalieva I.А., Bushueva Т.V., Shelomentsev I.G., Klinova S.V., Sakhautdinova R.R. Effects of selenium oxide nanoparticles on the morphofunctional state of the liver: experimental data. Health Risk Analysis, 2023, no. 1, pp. 147–156. DOI: 10.21668/health.risk/2023.1.14.eng
References: 
  1. Katsnelson B.A., Privalova L.I., Sutunkova M.P., Minigalieva I.A., Gurvich V.B., Shur V.Ya., Shishkina E.V., Ma-keyev O.H. [et al.]. Experimental research into metallic and metal oxide nanoparticle toxicity in vivo. Bioactivity of Engineered Nanoparticles, 2017, chapter 11, pp. 259–319.
  2. Maroney M.J., Hondal R.J. Selenium versus sulfur: Reversibility of chemical reactions and resistance to permanent oxidation in proteins and nucleic acids. Free Radic. Biol. Med., 2018, vol. 127, pp. 228–237. DOI: 10.1016/j.freeradbiomed.2018.03.035
  3. Mercan Y.U., Başbuğan Y., Uyar A., Kömüroğlu A.U., Keleş Ö.F. Use of an antiarrhythmic drug against acute sele-nium toxicity. J. Trace Elem. Med., 2020, vol. 59, pp. 126471. DOI: 10.1016/j.jtemb.2020.126471
  4. Misra S., Boylan M., Selvam A., Spallholz J.E., Björnstedt M. Redox-active selenium compounds – from toxicity and cell death to cancer treatment. Nutrients, 2015, vol. 7, no. 5, pp. 3536–3556. DOI: 10.3390/nu7053536
  5. Poluboyarinov P.A., Elistratov D.G., Shvets V.I. Metabolism and mechanism of toxicity of selenium-containing supplements used for optimizing human selenium status. Tonkie khimicheskie tekhnologii, 2019, vol. 14, no. 1, pp. 5–24. DOI: 10.32362/2410-6593-2019-14-1-5-24 (in Russian).
  6. Steinbrenner H., Duntas L.H., Rayman M.P. The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities. Redox Biol., 2022, vol. 50, pp. 102236. DOI: 10.1016/j.redox.2022.102236
  7. Vinceti M., Mandrioli J., Borella P., Michalke B., Tsatsakis A., Finkelstein Y. Selenium neurotoxicity in humans: Bridging laboratory and epidemiologic studies. Toxicol. Lett., 2014, vol. 230, no. 2, pp. 295–303. DOI: 10.1016/j.toxlet.2013.11.016
  8. Vinceti M., Chiari A., Eichmüller M., Rothman K.J., Filippini T., Malagoli C., Weuve J., Tondelli M. [et al.]. A sele-nium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment. Alzheimers Res. Ther., 2017, vol. 9, no. 1, pp. 100. DOI: 10.1186/s13195-017-0323-1
  9. Diskin C.J., Tomasso C.L., Alper J.C., Glase M.L., Fliegel S.E. Long-term selenium exposure. Arch. Intern. Med., 1979, vol. 139, no. 7, pp. 824–826.
  10. Shang N., Wang X., Shu Q., Wang H., Zhao L. The Functions of Selenium and Selenoproteins Relating to the Liver Diseases. J. Nanosci. Nanotechnol., 2019, vol. 19, no. 4, pp.1875–1888. DOI: 10.1166/jnn.2019.16287
  11. Bano I., Skalickova S., Arbab S., Urbankova L., Horky P. Toxicological effects of nanoselenium in animals. J. Anim. Sci. Biotechnol., 2022, vol. 13, no. 1, pp. 72. DOI: 10.1186/s40104-022-00722-2
  12. Zhang J., Wang H., Yan X., Zhang L. Comparison of short-term toxicity between Nano-Se and selenite in mice. Life Sci., 2005, vol. 76, no. 10, pp. 1099–1109. DOI: 10.1016/j.lfs.2004.08.015
  13. Wang H., Zhang J., Yu H. Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice. Free Radic. Biol. Med., 2007, vol. 42, no. 10, pp. 1524–1533. DOI: 10.1016/j.freeradbiomed.2007.02.013
  14. Zhang J., Wang X., Xu T. Elemental Selenium at Nano Size (Nano-Se) as a Potential Chemopreventive Agent with Reduced Risk of Selenium Toxicity: Comparison with Se-Methylselenocysteine in Mice. Toxicol. Sci., 2008, vol. 101, no. 1, pp. 22–31. DOI: 10.1093/toxsci/kfm221
  15. Urbankova L., Skalickova S., Pribilova M., Ridoskova A., Pelcova P., Skladanka J., Horky P. Effects of Sub-Lethal Doses of Selenium Nanoparticles on the Health Status of Rats. Toxics, 2021, vol. 9, no. 2, pp. 28. DOI: 10.3390/toxics9020028
  16. Zhang Z., Du Y., Liu T., Wong K.H., Chen T. Systematic acute and subchronic toxicity evaluation of polysaccharide-protein complex-functionalized selenium nanoparticles with anticancer potency. Biomater. Sci., 2019, vol. 7, no. 12, pp. 5112–5123. DOI: 10.1039/c9bm01104h
  17. He Y., Chen S., Liu Z., Cheng C., Li H., Wang M. Toxicity of selenium nanoparticles in male Sprague-Dawley rats at supranutritional and nonlethal levels. Life Sci., 2014, vol. 115, no. 1–2, pp. 44–51. DOI: 10.1016/j.lfs.2014.08.023
  18. Loeschner K., Hadrup N., Hansen M., Pereira S.A., Gammelgaard B., Møller L.H., Mortensen A., Lam H.R., Larsen E.H. Absorption, distribution, metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats. Metallomics, 2014, vol. 6, no. 2, pp. 330–337. DOI: 10.1039/c3mt00309d
  19. Lesnichaya M., Shendrik R., Titov E., Sukhov B. Synthesis and comparative assessment of antiradical activity, toxicity, and biodistribution of κ-carrageenan-capped selenium nanoparticles of different size: in vivo and in vitro study. IET nanobi-otechnology, 2020, vol. 14, no. 6, pp. 519–526. DOI: 10.1049/iet-nbt.2020.0023
  20. Fernandes A.P., Gandin V. Selenium compounds as therapeutic agents in cancer. Biochim. Biophys. Acta, 2015, vol. 1850, no. 8, pp. 1642–1660. DOI: 10.1016/j.bbagen.2014.10.008
  21. Nartsissov R.P. Primenenie n-nitrotetrazoli fioletovogo dlya kolichestvennoi tsitokhimii degidrogenaz limfotsitov cheloveka [Application of n-nitrotetrazole violet for quantitative cytochemistry of human lymphocyte dehydrogenases]. Arkhiv anatomii, gistologii i embriologii, 1969, vol. 56, no. 5, pp. 85–91 (in Russian).
  22. Sun M.G., Williams J., Munoz-Pinedo C., Perkins G.A., Brown J.M., Ellisman M.H., Green D.R., Frey T.G. Corre-lated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis. Nat. Cell Biol., 2007, vol. 9, no. 9, pp. 1057–1065. DOI: 10.1038/ncb1630
  23. Wojtczak L. Effect of long-chain fatty acids and acyl-CoA on mitochondrial permeability, transport, and energy-coupling processes. J. Bioenerg. Biomembr., 1976, vol. 8, no. 6, pp. 293–311. DOI: 10.1007/BF00765158
  24. Su X., Han X., Mancuso D.J., Abendschein D.R., Gross R.W. Accumulation of long-chain acylcarnitine and 3-hydroxy acylcarnitine molecular species in diabetic myocardium:  identification of alterations in mitochondrial fatty acid processing in dia-betic myocardium by shotgun lipidomics. Biochemistry, 2005, vol. 44, no. 13, pp. 5234–5245. DOI: 10.1021/bi047773a
  25. Violante S., Ijlst L., Te Brinke H., Tavares de Almeida I., Wanders R.J.A., Ventura F.V., Houten S.M. Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines. FASEB J., 2013, vol. 27, no. 5, pp. 2039–2044. DOI: 10.1096/fj.12-216689
  26. Fernandes J., Hu X., Ryan Smith M., Go Y.-M., Jones D.P. Selenium at the redox interface of the genome, metabolome and exposome. Free Radic. Biol. Med., 2018, vol. 127, pp. 215–227. DOI: 10.1016/j.freeradbiomed.2018.06.002
  27. Wu T., Tang M. Review of the effects of manufactured nanoparticles on mammalian target organs. J. Appl. Toxicol., 2018, vol. 38, no. 1, pp. 25–40. DOI: 10.1002/jat.3499
  28. Joles J.A., Stroes E.S., Rabelink T.J. Endothelial function in proteinuric renal disease. Kidney Int. Suppl., 1999, vol. 71, pp. S57–S61. DOI: 10.1046/j.1523-1755.1999.07115.x
  29. Tan S.T., Ramesh T., Toh X.R., Nguyen L.N. Emerging roles of lysophospholipids in health and disease. Progress in Lipid Research, 2020, vol. 80, pp. 101068. DOI: 10.1016/j.plipres.2020.101068
  30. Qin X., Qiu C., Zhao L. Lysophosphatidylcholine perpetuates macrophage polarization toward classically activated phenotype in inflammation. Cell. Immunol., 2014, vol. 289, no. 1–2, pp. 185–190. DOI: 10.1016/j.cellimm.2014.04.010
  31. Lauber K., Bohn E., Kröber S.M., Xiao Y., Blumenthal S.G., Lindemann R.K., Marini P., Wiedig C. [et al.]. Apoptotic Cells Induce Migration of Phagocytes via Caspase-3-Mediated Release of a Lipid Attraction Signal. Cell, 2003, vol. 113, no. 6, pp. 717–730. DOI: 10.1016/S0092-8674(03)00422-7
  32. Yamamoto Y., Sakurai T., Chen Z., Inoue N., Chiba H., Hui S.-P. Lysophosphatidylethanolamine Affects Lipid Accu-mulation and Metabolism in a Human Liver-Derived Cell Line. Nutrients, 2022, vol. 14, no. 3, pp. 579. DOI: 10.3390/nu14030579
  33. Darnell J.C., Osterman D.G., Saltiel A.R. Synthesis of phosphatidylinositol in rat liver microsomes is accompanied by the rapid formation of lysophosphatidylinositol. Biochim. Biophys. Acta, 1991, vol. 1084, no. 3, pp. 269–278. DOI: 10.1016/0005-2760(91)90069-t
  34. Poccia D.L., Larijani B. Phosphatidylinositol metabolism and membrane fusion. Biochem. J., 2009, vol. 418, no. 2, pp. 233–246. DOI: 10.1042/bj20082105
  35. Piñeiro R., Falasca M. Lysophosphatidylinositol signalling: New wine from an old bottle. Biochim. Biophys. Acta, 2012, vol. 1821, no. 4, pp. 694–705. DOI: 10.1016/j.bbalip.2012.01.009
  36. Arifin S.A., Falasca M. Lysophosphatidylinositol Signalling and Metabolic Diseases. Metabolites, 2016, vol. 6, no. 1, pp. 6. DOI: 10.3390/metabo6010006
  37. Makide K., Uwamizu A., Shinjo Y., Ishiguro J., Okutani M., Inoue A., Aoki J. Novel lysophosphoplipid receptors: their structure and function. J. Lipid Res., 2014, vol. 55, no. 10, pp.1986–1995. DOI: 10.1194/jlr.R046920
  38. Fondevila M.F., Fernandez U., Gonzalez-Rellan M.J., Da Silva Lima N., Buque X., Gonzalez-Rodriguez A., Alonso C., Iruarrizaga-Lejarreta M. [et al.]. The L-α-Lysophosphatidylinositol/G Protein-Coupled Receptor 55 System Induces the Development of Nonalcoholic Steatosis and Steatohepatitis. Hepatology, 2021, vol. 73, no. 2, pp. 606–624. DOI: 10.1002/hep.31290
  39. Calvillo-Robledo A., Cervantes-Villagrana R.D., Morales P., Marichal-Cancino B.A. The oncogenic lysophosphati-dylinositol (LPI)/GPR55 signaling. Life Sci., 2022, vol. 301, pp. 120596. DOI: 10.1016/j.lfs.2022.120596
Received: 
15.09.2022
Approved: 
03.02.2023
Accepted for publication: 
10.03.2023

You are here