Increasing the resistance of the body to adverse cytotoxic effects of amorphous silicon dioxide nanoparticles

Introduction: Amorphous silicon dioxide nanoparticles of (SiNPs) are among the most common nanomaterials today. Besides, industrial aerosols formed by condensation and containing a significant proportion of SiNPs are spontaneously produced by a number of pyrometallurgical and welding processes. A significant number of individuals are therefore exposed to SiNPs in the occupational setting or polluted ambient air and while using this nanomaterial. The purpose of our experimental study was to develop a preventive method promoting the resistance of the organism to adverse cytotoxic effects of amorphous silicon dioxide nanoparticles. Materials and methods: White laboratory rats received a monthly course of a specially developed bioprophylactic complex (BPC) before a single intratracheal instillation of a SiNPs suspension at a concentration of 0.5 mg/mL. The suspension was obtained by laser ablation of thin sheet targets of the appropriate material of 99.99 % purity in sterile deionized water. The average diameter of SiNPs was 43 ± 11 nm. Cytological (the number of bronchoalveolar macrophages and neutrophils and their ratio) and cytochemical indices of the bronchoalveolar lavage (BAL) fluid (alkaline phosphatase, alanine aminotransferase, gamma-glutamyl transpeptidase, amylase, and lactate dehydrogenase) were evaluated at 24 hours after the injection. The bioprophylactic complex was administered to the animals with feed and drink and included monosodium glutamate, fish oil rich in omega-3 polyunsaturated fatty acids (PUFAs), iodine, and an antioxidant complex of selenium, quercetin (rutoside), and vitamins A, E, and C. Conclusions: Our findings show that changes in both cytological and biochemical BAL parameters proved a positive health effect of premedication that helped reduce cytotoxicity of SiNPs exposure.

amorphous silicon dioxide nanoparticles, cytotoxicity, bioprophylaxis

1. Сутункова М.П., Соловьева С.Н., Кацнельсон Б.А. и др. Некоторые особенности реакции организма на хроническую ингаляцию ЗЮ2-содержащих субмикронных (преимущественно наноразмерных) частиц реального промышленного аэрозоля // Токсикологический вестник. 2017. № 3 (144). С. 17-26.

2. Кацнельсон Б.А., Привалова Л.И., Сутункова М.П. и др. Биопрофилактика в системе управления профессиональными рисками, связанными с воздействием металлсодержащих наночастиц // Гигиена и санитария. 2017. Т. 96. № 12. С. 1187-1191.

3. Кацнельсон Б.А., Алексеева О.Г., Привалова Л.И. и др. Пневмокониозы: патогенез и биологическая профилактика. Екатеринбург: Издательство УрО РАН, 1995. 326 с.

4. Кацнельсон Б.А., Дегтярева Т.Д., Привалова Л.И. Принципы биологической профилактики профессиональной и экологически обусловленной патологии от воздействия неорганических веществ. Екатеринбург: МНЦПиОЗРП, 1999. 107 с.

5. Пластилина Ю.В., Привалова Л.И., Терешин Ю.С. и др. Тормозящее действие йода на развитие экспериментального силикоза при перкутанном воздействии // Медицина труда и пром. экология. 1996. № 7. С. 16-20.

6. Капелько В.И. Активные формы кислорода, антиоксиданты и профилактика заболеваний // Российский медицинский журнал. 2003. № 21. С. 1185-1189.

7. Денисенко С.А, Леканова С.С., Домнин С.Г и др. Прогнозирование действия пылевых частиц различных форм кремнезема на организм с учетом их физико-химических свойств. Пособие для врачей. Екатеринбург, 2003. 23 с.

8. Шапиро Н.А Цитологическая диагностика заболеваний легких. М.: Ретроцентр, 2005. 245 с.

9. Добрых В.А., Мун И.Е., Ковалева О.А. и др. Диагностическое значение цитологического исследования секрета нижних дыхательных путей // Дальневосточный медицинский журнал. 2013. № 1. С. 125-129.

10. Napierska D, Thomassen L, Lison D, et al. The nanosilica hazard: another variable entity. Part Fibre Toxicol. 2010; 7, 39. DOI: https://doi.org/10.1186/1743-8977-7-39

11. Vance ME, Kuiken T, Vejerano EP, et al. Nanotechnology in the real world: Redeveloping the nanomaterial consumer products inventory. Beilstein J Nanotechnol. 2015; 6:1769-1780. DOI: https://doi.org/10.3762/ bjnano.6.181

12. Thakkar A, Raval A, Chandra S, et al. A comprehensive review of the application of nano-silica in oil well cementing. Petroleum. 2019; 6(2):123-129. DOI: https:// doi.org/10.1016/j.petlm.2019.06.005

13. Shin-Woo Ha, Weiss D, Weitzmann M, et al. Applications of silica-based nanomaterials in dental and skeletal biology. In: Nanobiomaterials in Clinical Dentistry (Second Edition). Subramani K, Ahmed W, editors. Elsevier; 2019. P. 77-112. DOI: https://doi.org/10.1016/C2017-0-03524-3

14. Du Z, Zhao D, Jing L, et al. Cardiovascular toxicity of different sizes amorphous silica nanoparticles in rats after intratracheal instillation. Cardiovasc Toxicol. 2013; 13(3):194-207. DOI: https://doi.org/10.1007/s12012-013-9198-y

15. Guo C, Yang M, Jing L, et al. Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling. Int J Nanomedicine. 2016; 11:5257-5276. DOI: https://doi.org/10.2147/IJN.S112030

16. Park EJ, Park K. Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol Lett. 2009; 184(1):18-25. DOI: https:// doi.org/10.1016/j.toxlet.2008.10.012

17. Petrick L, Rosenblat M, Paland N, et al. Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation. Environ Toxicol. 2016; 31(6):713-723. DOI: https://doi.org/10.1002/tox.22084

18. Sergent JA, Paget V, Chevillard S. Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell line. Ann Occup Hyg. 2012; 56(5):622-630. DOI: https://doi.org/10.1093/annhyg/mes005

19. Privalova LI, Katsnelson BA, Sutunkova MP, et al. Looking for biological protectors against adverse health effects of some nanoparticles that can pollute workplace and ambient air (a summary of authors’ experimental results). J Environ Prot. 2017; 8(8):844-866. DOI: https:// doi.org/10.4236/jep.2017.88053

20. Katsnelson BA, Privalova LI, Sutunkova MP, et al. Experimental research into metallic and metal oxide nanoparticle toxicity in vivo. In: Bioactivity of engineered nanoparticles. Yan B, Zhou H, Gardea-Torresdey J, editors. Springer, 2017. Ch. 11. P. 259-319. DOI: https://doi.org/10.1007/978-981-10-5864-6

21. Katsnelson BA, Morosova KI, Velichkovski BT, et al. Anti-silikotische Wirkung von Glutamat. Arbeitsmed. Sozialmed. Praventivmed. 1984; 19(7):153-156. (In German).

22. Morosova KI, Katsnelson BA, Rotenberg YuS, et al. A further experimental study of the antisilicotic effect of glutamate. Br J Ind Med. 1984; 41(4):518-525.

23. Katsnelson BA, Polzik EV, Privalova LI. Some aspects of the problem of individual predisposition to silicosis. Environ Health Perspect. 1986; 68:175-185.

24. Katsnelson BA, Polzik EV, Morosova KI, et al. Trends and perspectives of the biological prophylaxis of silicosis. Environ Health Pespect. 1989; 82:311-321.

25. Li X, Jin Q, Yao Q, et al. The flavonoid quercetin ameliorates liver inflammation and fibrosis by regulating hepatic macrophages activation and polarization in mice. Front Pharmacol. 2018; 9:72. DOI: https://doi. org/10.3389/fphar.2018.00072