morphoМорфологические ведомостиMorphological newsletter1812-31712686-8741Private Medical University REAVIZ10.20340/mv-mn.17(25).03.37-42morpho-67Research ArticleМОРФОМИКА - НОВЫЕ ТЕХНОЛОГИИPART 3 - MORPHOMICS - NEW TECHNOLOGIESИССЛЕДОВАНИЕ ЭМБРИОТОКСИЧЕСКОГО ДЕЙСТВИЯ НАНОЧАСТИЦ ДИОКСИДА ТИТАНА НА КРЫСTHE STUDY OF EMBRYOTOXIC EFFECT OF TITANIUM DIOXIDE NANOPERTICLES ON RATSШарафутдиноваЛ. А.SharafutdinovaL. A.sharafla@yandex.ruХисматуллинаЗ. Р.KhismatullinaZ. R.hismatullinazr@mail.ruДаминовМ. Р.DaminovM. R.sharafla@yandex.ruВалиуллинВ. В.ValiullinV. V.valvv@kcn.ruБашкирский государственный университетРоссияBashkir State UniversityRussian FederationКазанский государственный медицинский университетРоссияKazan State Medical UniversityRussian Federation2017300920172533742Copyright © Шарафутдинова Л.А., Хисматуллина З.Р., Даминов М.Р., Валиуллин В.В., 20172017Шарафутдинова Л.А., Хисматуллина З.Р., Даминов М.Р., Валиуллин В.В.Sharafutdinova L.A., Khismatullina Z.R., Daminov M.R., Valiullin V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.morpholetter.com/jour/article/view/67

Широкое использование наноматериалов в различных отраслях деятельности человека приводит к возникновению ряда проблем. Хорошо известно, что некоторые наноматериалы могут обладать эмбриотоксическим эффектом, оказывая прямое воздействие на плод после проникновения через плацентарный барьер. Цель настоящего исследования - оценить на основе изучения предимплантационной и постимлантационной смертности и особенностей постнатального развития эмбриотоксические свойства нанодисперсного диоксида титана (TO2) при пероральном введении. Показано, что пероральное введение нанодисперсного диоксида титана в дозе 50 мг/кг беременным самкам крыс с 1-го по 19-й день беременности оказывает выраженное эмбриотоксическое действие, выраженное в повышении предимплантационной, постимплантационной и общей эмбриональной смертности плодов. Изучены отдаленные эффекты антенатального воздействия нанодисперсного диоксида титана на развитие потомства крыс в раннем постанатальном периоде онтогенеза, в первые 30 дней жизни. Установлено повышение смертности крысят в период вскармливания, отставание их в весе и задержка морфофункционального созревания на постнатальном этапе онтогенеза. Таким образом, несмотря на существование биологических барьеров, которые в целом достаточно эффективно защищают развивающийся организм, исследованные нами наночастицы диоксида титана, по-видимому, оказывают существенные эмбриотоксические эффекты, в том числе отсроченные по их проявлению у подвергшегося воздействию потомства.

The widespread use of nanomaterials in various fields of human activity leads to a number of problems. It is well known that some nanomaterials may have an embryotoxic effect, having a direct effect on the fetus at penetrating through placental barrier. The purpose of this study is to evaluate, on the basis of the study of pre-implantational and post-implantational mortality and features of postnatal development, the embryotoxic properties of nanodispersed titanium dioxide (TiO2) when administered orally. It has been shown that oral administration of 50 mg/kg nanodispersed titanium dioxide to pregnant female rats from the 1st to 19th day of pregnancy has a pronounced embryotoxic effect, expressed in an increase in pre-implantational, post-implantational and total embryonic fetal mortality. The long-term effects of the antenatal effect of nanodispersed titanium dioxide on the development of the offspring of rats in the early postnatal period of ontogenesis were studied in the first 30 days of life. An increase in the death rate of rats during the feeding period, a delay in their weight and a delay in morphological and functional maturation in the postnatal stage of ontogenesis have been established. Thus, in spite of the existence of biological barriers, which in general sufficiently effectively protect the developing organism, the titanium dioxide nanoparticles investigated by us seem to have significant embryotoxic effects, including those delayed in their manifestation in the exposed offspring.

наночастицыдиоксид титанаэмбриотоксичностькрысаnanoparticlestitanium dioxideembryotoxicityratReferencesOberdorster G. Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health. 2001; 74 (1): 8.Oberdorster G. Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health. 2001; 74 (1): 8.Kaida T., Kobayashi K., Adachi M., Suzuki F. Optical characteristics of titanium oxide interference film and the film laminated with oxides and their applications for cosmetics. J Cosmet Sci. 2004; 55: 219-220.Kaida T., Kobayashi K., Adachi M., Suzuki F. Optical characteristics of titanium oxide interference film and the film laminated with oxides and their applications for cosmetics. J Cosmet Sci. 2004; 55: 219-220.Wang J.J., Sanderson B.J., Wang H. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res. 20076289 (99): 106.Wang J.J., Sanderson B.J., Wang H. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res. 20076289 (99): 106.Wolf R., Matz H., Orion E., Lipozencic J. Sunscreens - the ultimate cosmetic. Acta Dermatovenerol Croat. 2003; 11: 158-162.Wolf R., Matz H., Orion E., Lipozencic J. Sunscreens - the ultimate cosmetic. Acta Dermatovenerol Croat. 2003; 11: 158-162.Baan R., Straif K., Grosse Y., et al. Carcinogenicity of carbon black, titanium dioxide, and talc. Lancet Oncol. 2006; 7: 295-296.Baan R., Straif K., Grosse Y., et al. Carcinogenicity of carbon black, titanium dioxide, and talc. Lancet Oncol. 2006; 7: 295-296.Robertson T.A., Sanchez W.Y., Roberts M.S. Are commercially available nanoparticles safe when applied to the skin? J Biomed Nanotechnol. 2010; 6: 452-468.Robertson T.A., Sanchez W.Y., Roberts M.S. Are commercially available nanoparticles safe when applied to the skin? J Biomed Nanotechnol. 2010; 6: 452-468.EU - European Commission Recommendation on the definition of nanomaterial. URL: http://osha.europa.eu/en/news/eu-european-commissionrecommendation-on-the-definition-of-nanomaterial. Date of request 30/09/2017.EU - European Commission Recommendation on the definition of nanomaterial. URL: http://osha.europa.eu/en/news/eu-european-commissionrecommendation-on-the-definition-of-nanomaterial. Date of request 30/09/2017.American Conference of Governmental Industrial Hygienists (ACGIH): Threshold limit values and biological exposure indices for 1992-1993. Cincinnati: Ohio: American Conference of Governmental industrial hygienists, 1992.American Conference of Governmental Industrial Hygienists (ACGIH): Threshold limit values and biological exposure indices for 1992-1993. Cincinnati: Ohio: American Conference of Governmental industrial hygienists, 1992.Weir A., Westerhoff P., Fabricius L., Hristovski K., von Goetz N. Titanium dioxide nanoparticles in food and personal care products. Environ SciTechnol. 2012; 46: 2242-2250.Weir A., Westerhoff P., Fabricius L., Hristovski K., von Goetz N. Titanium dioxide nanoparticles in food and personal care products. Environ SciTechnol. 2012; 46: 2242-2250.Yuan Y., Ding J., Xu J., Deng J., Guo J. TiO2 nanoparticles co-doped with silver and nitrogen for antibacterial application. J Nanosci Nanotechnol. 2010; 10: 4868-4874.Yuan Y., Ding J., Xu J., Deng J., Guo J. TiO2 nanoparticles co-doped with silver and nitrogen for antibacterial application. J Nanosci Nanotechnol. 2010; 10: 4868-4874.Risk Science Institute Workshop Participants ILSI. The relevance of the rat lung response to particle overload for human risk assessment: A workshop consensus report. Inhal Toxicol. 2000; 12: 1-17.Risk Science Institute Workshop Participants ILSI. The relevance of the rat lung response to particle overload for human risk assessment: A workshop consensus report. Inhal Toxicol. 2000; 12: 1-17.Zhao J., Bowman L., Zhang X., et al. Titanium dioxide (TiO2) nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways. J Toxicol Environ Health A. 2009; 72: 1141-1149.Zhao J., Bowman L., Zhang X., et al. Titanium dioxide (TiO2) nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways. J Toxicol Environ Health A. 2009; 72: 1141-1149.Lee K.P., Trochimowicz H.J., Reinhardt C.F. Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol Appl Pharmacol. 1985; 79: 179-192.Lee K.P., Trochimowicz H.J., Reinhardt C.F. Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol Appl Pharmacol. 1985; 79: 179-192.Hongbo S., Ruth M., Vincent C., Jinsbun Z. Titanium dioxide nanoparticles: a review of current toxicological data. Particle and Fibre Toxicology. 2013; 10(15): 1-33.Hongbo S., Ruth M., Vincent C., Jinsbun Z. Titanium dioxide nanoparticles: a review of current toxicological data. Particle and Fibre Toxicology. 2013; 10(15): 1-33.Songo B., Liu J., Feng X., Wi L., Shao L. A review on potential neurotoxicity of titanium dioxide nanoparticles. Nanoscale res Lett. 2015; 10(1): 1042.Songo B., Liu J., Feng X., Wi L., Shao L. A review on potential neurotoxicity of titanium dioxide nanoparticles. Nanoscale res Lett. 2015; 10(1): 1042.Syed N.S., Zahir S., Muzammal H., Muzaffar K. Hazardous Effects of Titanium Dioxide Nanoparticles in Ecosystem. Bioinorganic Chemistry and Applications. 2017; doi.org/10.1155/2017/4101735.Syed N.S., Zahir S., Muzammal H., Muzaffar K. Hazardous Effects of Titanium Dioxide Nanoparticles in Ecosystem. Bioinorganic Chemistry and Applications. 2017; doi.org/10.1155/2017/4101735.MU 1.2.2520_09 Toksikologo-gigienicheskaya otsenka bezopasnosti nanomaterialov. M., 2007. URL: https://ohranatruda.ru/ot_biblio/normativ/data_normativ/57/57354/Date of request 30/09/2017.MU 1.2.2520_09 Toksikologo-gigienicheskaya otsenka bezopasnosti nanomaterialov. M., 2007. URL: https://ohranatruda.ru/ot_biblio/normativ/data_normativ/57/57354/Date of request 30/09/2017.Lang E.A. Kak opisyvat' statistiku v meditsine. Annotirovannoe rukovodstvo dlya avtorov, redaktorov i retsenzentov. M.: prakticheskaya meditsina, 2011. 480s.Lang E.A. Kak opisyvat' statistiku v meditsine. Annotirovannoe rukovodstvo dlya avtorov, redaktorov i retsenzentov. M.: prakticheskaya meditsina, 2011. 480s.Petri A., Sebin K. Naglyadnaya statistika v meditsine. M.: GEOTAR-media, 2003. 144s.Petri A., Sebin K. Naglyadnaya statistika v meditsine. M.: GEOTAR-media, 2003. 144s.Mazur I.A., Voloshin N.A., Grigor'eva E.A. i dr. Doklinicheskoe issledovanie embriotoksichnosti i teratogennosti preparata liziniy. Patologiya. 2011; 8(2): 85-88.Mazur I.A., Voloshin N.A., Grigor'eva E.A. i dr. Doklinicheskoe issledovanie embriotoksichnosti i teratogennosti preparata liziniy. Patologiya. 2011; 8(2): 85-88.Bokov D.A., Neverova P.S., Obidchenko M.P., Senchukova M.A., Shevlyuk N.N. Eksperimental'noe modelirovanie toksigennoy patologii embriogeneza: ekologicheskie aspekty. Vestnik Orenburgskogo universiteta. 2015; 10(185): 203-207.Bokov D.A., Neverova P.S., Obidchenko M.P., Senchukova M.A., Shevlyuk N.N. Eksperimental'noe modelirovanie toksigennoy patologii embriogeneza: ekologicheskie aspekty. Vestnik Orenburgskogo universiteta. 2015; 10(185): 203-207.Shimizu M., Tainaka H., Oba T., et al. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part Fibre Toxicol. 2009; 6: 20.Shimizu M., Tainaka H., Oba T., et al. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part Fibre Toxicol. 2009; 6: 20.Engler-Chiurazzi E.B., Stapleton P.A., et al. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition. J. Toxicol Environ Health A. 2016; 79(11): 447-52.Engler-Chiurazzi E.B., Stapleton P.A., et al. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition. J. Toxicol Environ Health A. 2016; 79(11): 447-52.Mohammadipour A., Fazel A., Haghir H., et al. Maternal exposure to Titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation I rat offspring. Environ. Toxicol. Pharmacol. 2014; 37(2): 617-25.Mohammadipour A., Fazel A., Haghir H., et al. Maternal exposure to Titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation I rat offspring. Environ. Toxicol. Pharmacol. 2014; 37(2): 617-25.Tochilkina L.P., Bocharova L.Yu., Sroslov M.S., Filatov B.N., Khodykina N.V. Eksperimental'noe issledovanie embriotoksichnosti nanochastits dioksida titana. Meditsina ekstremal'nykh situatsiy. 2014; 4(50): 48-58.Tochilkina L.P., Bocharova L.Yu., Sroslov M.S., Filatov B.N., Khodykina N.V. Eksperimental'noe issledovanie embriotoksichnosti nanochastits dioksida titana. Meditsina ekstremal'nykh situatsiy. 2014; 4(50): 48-58.Mikheeva N.A., Ryzhova M.V., Nikiforov R.V., Terentyuk G.S., Khlebtsov N.G., Khayrullin R.M. Pronitsaemost' gemato-platsentarnogo bar'era belykh krys dlya zolotykh nanochastits // Rossiyskiy bioterapevticheskiy zhurnal. - 2011. - T. 10. - № 4. - S. 113.Mikheeva N.A., Ryzhova M.V., Nikiforov R.V., Terentyuk G.S., Khlebtsov N.G., Khayrullin R.M. Pronitsaemost' gemato-platsentarnogo bar'era belykh krys dlya zolotykh nanochastits // Rossiyskiy bioterapevticheskiy zhurnal. - 2011. - T. 10. - № 4. - S. 113.Tsyganova N.A., Khayrullin R.M., Terentyuk G.S., Khlebtsov B.N., Bogatyrev V.A., Dykman L.A., Erykov S.N., Khlebtsov N.G. Pronitsaemost' pegilirovannykh zolotykh nanochastits cherez gematoplatsentarnyy bar'er krys // Byulleten' eksperimental'noy biologii i meditsiny. - 2014. - T. 157. - № 3. - S. 366-369.Tsyganova N.A., Khayrullin R.M., Terentyuk G.S., Khlebtsov B.N., Bogatyrev V.A., Dykman L.A., Erykov S.N., Khlebtsov N.G. Pronitsaemost' pegilirovannykh zolotykh nanochastits cherez gematoplatsentarnyy bar'er krys // Byulleten' eksperimental'noy biologii i meditsiny. - 2014. - T. 157. - № 3. - S. 366-369.Mikheeva N.A., Khayrullin R.M. Pronitsaemost' nanochastits cherez gematoplatsentarnyy bar'er/ V kn.: Sovremennaya meditsina: traditsii i innovatsii. Sb. st. II Mezhdunar. nauch.-prakt. konf.- Ekaterinburg: Izdatel'sko-poligraficheskoe predpriyatie ''Maks-Info'', 2017. - S. 26-30.Mikheeva N.A., Khayrullin R.M. Pronitsaemost' nanochastits cherez gematoplatsentarnyy bar'er/ V kn.: Sovremennaya meditsina: traditsii i innovatsii. Sb. st. II Mezhdunar. nauch.-prakt. konf.- Ekaterinburg: Izdatel'sko-poligraficheskoe predpriyatie ''Maks-Info'', 2017. - S. 26-30.

The authors declare that there are no conflicts of interest present.