nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»10.31146/1682-8658-ecg-244-12-186-192nogr-3299Research ArticleЭКСПЕРИМЕНТАЛЬНАЯ ГАСТРОЭНТЕРОЛОГИЯEXPERIMENTAL GASTROENTEROLOGYАнализ морфологических и морфометрических характеристик стенки желудка мышей при пероральном введении наночастиц оксида железаAnalysis of morphological and morphometric characteristics of the mouse stomach wall after oral administration of iron oxide nanoparticleshttps://orcid.org/0000-0001-8134-0899КирееваА. В.KireevaA. V.noemail@neicon.ruhttps://orcid.org/0000-0001-9552-447XКоленчуковаО. А.KolenchukovaO. A.noemail@neicon.ruhttps://orcid.org/0000-0002-7650-0170БирюковаЕ. А.BiryukovaE. A.helena.biryukova.1996@gmail.comФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр «Красноярский научный центр Сибирского отделения Российской академии наук»РоссияKrasnoyarsk Science Centre of the Siberian Branch of Russian Academy of ScienceRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр «Красноярский научный центр Сибирского отделения Российской академии наук», обособленное подразделение «Научно-исследовательский институт медицинских проблем Севера; Федеральное государственное бюджетное образовательное учреждение высшего образования «Красноярский государственный аграрный университетРоссияScientific Research Institute of Medical Problems of the North Federal Research Center Krasnoyarsk Science Centre of the Siberian Branch of Russian Academy of Science; Krasnoyarsk state agricultural universityRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр «Красноярский научный центр Сибирского отделения Российской академии наук», обособленное подразделение «Научно-исследовательский институт медицинских проблем СевераРоссияScientific Research Institute of Medical Problems of the North Federal Research Center Krasnoyarsk Science Centre of the Siberian Branch of Russian Academy of ScienceRussian Federation202526022026012186192Copyright © Киреева А.В., Коленчукова О.А., Бирюкова Е.А., 20262026Киреева А.В., Коленчукова О.А., Бирюкова Е.А.Kireeva A.V., Kolenchukova O.A., Biryukova E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nogr.org/jour/article/view/3299

Наночастицы оксида железа привлекают внимание в научной среде из-за широкого спектра их уникальных физико-химических свойств, получаемых в ходе различных методов синтеза. Однако их воздействие на организм при пероральном введении изучено недостаточно. Цель исследования - изучение морфологических и морфометрических характеристик слизистой оболочки желудка лабораторных мышей при использовании синтетических и биогенных наночастиц оксида железа в качестве кормовой добавки. Материалы и методы. В работе были использованы синтетические (без оболочки) и биогенные (инкапсулированные) наночастицы оксида железа. Исследование проводилось на лабораторных мышах (55 особей), разделенных на 3 группы. 1 группа мышей (15 особей) - интактные животные, получавшие стандартное кормление; 2 группа (20 особей) получала корм с синтетическими наночастицами; 3 группа (20 особей) получала корм с биогенными наночастицами. Длительность эксперимента составляла 36 суток. Забор образцов осуществляли на 1, 22 и 36 сутки. Окрашивание гистологических срезов осуществляли гематоксилин-эозином и по Перлсу. Морфометрический анализ препаратов выполнялся в программе «ВиодеоТесТ - Морфология 7.0». Результаты. При пероральном поступлении в организм наночастиц оксида железа в обеих группах обнаружены следующие патологические изменения слизистой оболочки желудка: лимфогистиоцитарная инфильтрация, кровоизлияния, расширение желудочных желез, кисты и дистрофические изменения клеток поверхностного эпителия. При этом у животных 3 группы на 36 сутки отмечались очаги атрофического гастрита и выраженные очаги деструкции желудочных желез. Заключение. Поступление как синтетических, так и биогенных наночастиц оксида железа в желудочно-кишечный тракт в течение 36 дней вызывают патологические изменения ткани желудка в виде метаплазии эпителия с дистрофическими изменениями в желудочных железах.

Iron oxide nanoparticles attract attention in the scientific community due to the wide range of their unique physico-chemical properties obtained during various synthesis methods. However, their effects on the body when administered orally have not been sufficiently studied. This work was aimed to study of morphological and morphometric characteristics of the gastric mucosa of laboratory mice using synthetic and biogenic iron oxide nanoparticles as a feed additive. Materials and methods. Nanoparticles of synthetic and biogenic iron origin were used in the work. The laboratory mice (n = 55) were allocated into 3 groups: 1 group of mice (n = 15) were intact animals that received standard feeding; group 2 (n = 20) fed food with synthetic nanoparticles; group 3 (n = 20) fed food with biogenic nanoparticles. The biological material (mouse stomach) was sampled on days 1, 22, and 36. Histological sections were stained with hematoxylin-eosin and Perls. Morphometric analysis of the drugs was performed in the program “ViodeoTesT - Morphology 7.0”. Results. Upon oral administration of iron oxide nanoparticles into the body, lymphohistiocytic infiltration, hemorrhages, enlargement of the gastric glands, cysts, and dystrophic changes in the cells of the columnar epithelium were detected in both groups. At the same time, foci of atrophic gastritis and pronounced foci of destruction of the gastric glands were noted in animals of group 3 on day 36. Conclusion. The entry of both synthetic and biogenic iron oxide nanoparticles into the gastrointestinal tract for 36 days causes pathological changes in the stomach tissue in the form of epithelial metaplasia with dystrophic changes in the gastric glands.

наночастицы оксида железа синтетическиенаночастицы оксида железа биогенныестенка желудкаморфометрияморфологияsynthetic iron nanoparticlesbiogenic iron nanoparticlesstomach wallmorphometrymorphologyReferencesZhang L., Zhao D. Applications of nanoparticles for brain cancer imaging and therapy. J Biomed Nanotechnol. 2014;10(9):1713-31. doi: 10.1166/jbn.2014.1896.Zhang L., Zhao D. Applications of nanoparticles for brain cancer imaging and therapy. J Biomed Nanotechnol. 2014;10(9):1713-31. doi: 10.1166/jbn.2014.1896.Mittal A., Roy I., Gandhi S. Magnetic nanoparticles: an overview for biomedical applications. Magnetochemistry. 2022;8(9):107. doi: 10.3390/magnetochemistry8090107.Mittal A., Roy I., Gandhi S. Magnetic nanoparticles: an overview for biomedical applications. Magnetochemistry. 2022;8(9):107. doi: 10.3390/magnetochemistry8090107.Öztürk K, Kaplan M., Çalış S. Effects of nanoparticle size, shape, and zeta potential on drug delivery.Int J Pharm. 2024;666:124799. doi: 10.1016/j.ijpharm.2024.124799.Öztürk K, Kaplan M., Çalış S. Effects of nanoparticle size, shape, and zeta potential on drug delivery.Int J Pharm. 2024;666:124799. doi: 10.1016/j.ijpharm.2024.124799.Hua S. Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors. Front Pharmacol. 2020;11:524. doi: 10.3389/fphar.2020.00524.Hua S. Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors. Front Pharmacol. 2020;11:524. doi: 10.3389/fphar.2020.00524.Ghosh R., Arcot J. Fortification of foods with nano-iron: its uptake and potential toxicity: current evidence, controversies, and research gaps. Nutr Rev. 2022;80(9):1974-84. doi: 10.1093/nutrit/nuac011.Ghosh R., Arcot J. Fortification of foods with nano-iron: its uptake and potential toxicity: current evidence, controversies, and research gaps. Nutr Rev. 2022;80(9):1974-84. doi: 10.1093/nutrit/nuac011.Voss L, Hsiao I.L., Ebisch M. et аl. The presence of iron oxide nanoparticles in the food pigment E172. Food Chem. 2020;327:127000. doi: 10.1016/j.foodchem.2020.127000.Voss L, Hsiao I.L., Ebisch M. et аl. The presence of iron oxide nanoparticles in the food pigment E172. Food Chem. 2020;327:127000. doi: 10.1016/j.foodchem.2020.127000.Zhang Q., Wu W., Zhang J., Xia X. Eradication of Helicobacter pylori: The power of nanosized formulations. Nanomedicine. 2020;15(5):527-542. doi: 10.2217/nnm-2019-0329.Zhang Q., Wu W., Zhang J., Xia X. Eradication of Helicobacter pylori: The power of nanosized formulations. Nanomedicine. 2020;15(5):527-542. doi: 10.2217/nnm-2019-0329.Zhu X., Su T., Wang S. et аl. New Advances in Nano-Drug Delivery Systems: Helicobacter pylori and Gastric Cancer. Front Oncol. 2022;12:834934. doi: 10.3389/fonc.2022.834934.Zhu X., Su T., Wang S. et аl. New Advances in Nano-Drug Delivery Systems: Helicobacter pylori and Gastric Cancer. Front Oncol. 2022;12:834934. doi: 10.3389/fonc.2022.834934.Date A.A., Hanes J., Ensign L.M. Nanoparticles for oral delivery: Design, evaluation and state-of-the-art. J Control Release. 2016;240:504-526. doi: 10.1016/j.jconrel.2016.06.016.Date A.A., Hanes J., Ensign L.M. Nanoparticles for oral delivery: Design, evaluation and state-of-the-art. J Control Release. 2016;240:504-526. doi: 10.1016/j.jconrel.2016.06.016.Maisel K., Ensign L., Reddy M. et аl. Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse. J Control Release. 2015;197:48-57. doi: 10.1016/j.jconrel.2014.10.026.Maisel K., Ensign L., Reddy M. et аl. Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse. J Control Release. 2015;197:48-57. doi: 10.1016/j.jconrel.2014.10.026.Banerjee A., Qi J., Gogoi R. et аl. Role of nanoparticle size, shape and surface chemistry in oral drug delivery. J Control Release. 2016;238:176-185. doi: 10.1016/j.jconrel.2016.07.051.Banerjee A., Qi J., Gogoi R. et аl. Role of nanoparticle size, shape and surface chemistry in oral drug delivery. J Control Release. 2016;238:176-185. doi: 10.1016/j.jconrel.2016.07.051.Garcia-Fernandez J., Turiel D., Bettmer J. et аl. In vitro and in situ experiments to evaluate the biodistribution and cellular toxicity of ultrasmall iron oxide nanoparticles potentially used as oral iron supplements. Nanotoxicology. 2020;14(3):388-403. doi: 10.1080/17435390.2019.1710613.Garcia-Fernandez J., Turiel D., Bettmer J. et аl. In vitro and in situ experiments to evaluate the biodistribution and cellular toxicity of ultrasmall iron oxide nanoparticles potentially used as oral iron supplements. Nanotoxicology. 2020;14(3):388-403. doi: 10.1080/17435390.2019.1710613.Egbuna C., Parmar V.K., Jeevanandam J. et al. Toxicity of nanoparticles in biomedical application: nanotoxicology. J Toxicol. 2021;9954443. doi: 10.1155/2021/9954443.Egbuna C., Parmar V.K., Jeevanandam J. et al. Toxicity of nanoparticles in biomedical application: nanotoxicology. J Toxicol. 2021;9954443. doi: 10.1155/2021/9954443.Stolyar S.V., Kolenchukova O.A., Boldyreva A.V. et al. Biogenic ferrihydrite nanoparticles: synthesis, properties in vitro and in vivo testing and the concentration effect. Biomedicines. 2021;9(3):323. doi: 10.3390/biomedicines9030323.Stolyar S.V., Kolenchukova O.A., Boldyreva A.V. et al. Biogenic ferrihydrite nanoparticles: synthesis, properties in vitro and in vivo testing and the concentration effect. Biomedicines. 2021;9(3):323. doi: 10.3390/biomedicines9030323.Mohamed E.K., Fathy M.M., Sadek N.A. et al. The effects of rutin coat on the biodistribution and toxicities of iron oxide nanoparticles in rats. J Nanopart Res. 26:49. doi: 10.1007/s11051-024-05949-w.Mohamed E.K., Fathy M.M., Sadek N.A. et al. The effects of rutin coat on the biodistribution and toxicities of iron oxide nanoparticles in rats. J Nanopart Res. 26:49. doi: 10.1007/s11051-024-05949-w.Göring J., Schwarz C., Unger E. et al. The Long-Term Impact of Polysaccharide-Coated Iron Oxide Nanoparticles on Inflammatory-Stressed Mice. J. Xenobiot. 2024;14:1711-1728. doi: 10.3390/jox14040091.Göring J., Schwarz C., Unger E. et al. The Long-Term Impact of Polysaccharide-Coated Iron Oxide Nanoparticles on Inflammatory-Stressed Mice. J. Xenobiot. 2024;14:1711-1728. doi: 10.3390/jox14040091.Vakili-Ghartavol R., Momtazi-Borojeni A.A., Vakili-Ghartavol Z. et al. Toxicity assessment of superparamagnetic iron oxide nanoparticles in different tissues. Artificial Cells, Nanomedicine, and Biotechnology. 2020;48(1):443-51. doi: 10.1080/21691401.2019.1709855.Vakili-Ghartavol R., Momtazi-Borojeni A.A., Vakili-Ghartavol Z. et al. Toxicity assessment of superparamagnetic iron oxide nanoparticles in different tissues. Artificial Cells, Nanomedicine, and Biotechnology. 2020;48(1):443-51. doi: 10.1080/21691401.2019.1709855.Kireeva A.V., Kolenchukova O.A., Biryukova E.A. et al. Effect of synthetic and biogenic iron oxide nanoparticles on histopathological parameters of mouse kidneys. J Evol Biochem Phys. 2025;61:261-72. doi: 10.1134/S0022093025010211.Kireeva A.V., Kolenchukova O.A., Biryukova E.A. et al. Effect of synthetic and biogenic iron oxide nanoparticles on histopathological parameters of mouse kidneys. J Evol Biochem Phys. 2025;61:261-72. doi: 10.1134/S0022093025010211.Chrishtop V.V., Mironov V.A., Prilepskii A.Y. et al. Organ-specific toxicity of magnetic iron oxide-based nanoparticles. Nanotoxicology. 2021;15(2):167-204. doi: 10.1080/17435390.2020.1842934.Chrishtop V.V., Mironov V.A., Prilepskii A.Y. et al. Organ-specific toxicity of magnetic iron oxide-based nanoparticles. Nanotoxicology. 2021;15(2):167-204. doi: 10.1080/17435390.2020.1842934.Strugari A.F.G., Stan M.S., Gharbia S. et al. Characterization of nanoparticle intestinal transport using an in vitro co-culture model. Nanomaterials (Basel). 2018;9(1):5. doi: 10.3390/nano9010005.Strugari A.F.G., Stan M.S., Gharbia S. et al. Characterization of nanoparticle intestinal transport using an in vitro co-culture model. Nanomaterials (Basel). 2018;9(1):5. doi: 10.3390/nano9010005.Chamorro S., Gutiérrez L., Vaquero M.P. et al. Safety assessment of chronic oral exposure to iron oxide nanoparticles. Nanotechnology. 2015;26(20):205101. doi: 10.1088/0957-4484/26/20/205101.Chamorro S., Gutiérrez L., Vaquero M.P. et al. Safety assessment of chronic oral exposure to iron oxide nanoparticles. Nanotechnology. 2015;26(20):205101. doi: 10.1088/0957-4484/26/20/205101.González A., Gálvez N., Martín J. et al. Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption. Food Chem. 2017;228:374-80. doi: 10.1016/j.foodchem.2017.02.008.González A., Gálvez N., Martín J. et al. Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption. Food Chem. 2017;228:374-80. doi: 10.1016/j.foodchem.2017.02.008.Skolmowska D., Głąbska D. Analysis of heme and non-heme iron intake and iron dietary sources in adolescent menstruating females in a national polish sample. Nutrients. 2019;11(5):1049. doi: 10.3390/nu11051049.Skolmowska D., Głąbska D. Analysis of heme and non-heme iron intake and iron dietary sources in adolescent menstruating females in a national polish sample. Nutrients. 2019;11(5):1049. doi: 10.3390/nu11051049.Skrypnik K., Bogdański P., Sobieska M. et al. Hepcidin and erythroferrone correlate with hepatic iron transporters in rats supplemented with multispecies probiotics. Molecules. 2020;25(7):1674. doi: 10.3390/molecules25071674.Skrypnik K., Bogdański P., Sobieska M. et al. Hepcidin and erythroferrone correlate with hepatic iron transporters in rats supplemented with multispecies probiotics. Molecules. 2020;25(7):1674. doi: 10.3390/molecules25071674.Portilla Y., Mellid S., Paradela A. et al. Iron oxide nanoparticle coatings dictate cell outcomes despite the influence of protein coronas. ACS Appl Mater Interfaces. 2021;13(7):7924-44. doi: 10.1021/acsami.0c20066.Portilla Y., Mellid S., Paradela A. et al. Iron oxide nanoparticle coatings dictate cell outcomes despite the influence of protein coronas. ACS Appl Mater Interfaces. 2021;13(7):7924-44. doi: 10.1021/acsami.0c20066.des Rieux A., Ragnarsson E.G., Gullberg E. et al. Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. Eur. J. Pharmaceut. Sci. 2005; 25(4-5):455-465. doi: 10.1016/j.ejps.2005.04.015.des Rieux A., Ragnarsson E.G., Gullberg E. et al. Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. Eur. J. Pharmaceut. Sci. 2005; 25(4-5):455-465. doi: 10.1016/j.ejps.2005.04.015.Carr K.E., Smyth S.H., McCullough M.T. et al. Morphological aspects of interactions between microparticles and mammalian cells: intestinal uptake and onward movement. Prog Histochem Cytochem. 2012;46(4):185-252. doi: 10.1016/j.proghi.2011.11.001.Carr K.E., Smyth S.H., McCullough M.T. et al. Morphological aspects of interactions between microparticles and mammalian cells: intestinal uptake and onward movement. Prog Histochem Cytochem. 2012;46(4):185-252. doi: 10.1016/j.proghi.2011.11.001.Wang X., Gong J., Tan W. et al. Adsorption of proteins on oral Zn2+ doped iron oxide nanoparticles in mouse stomach and in vitro: triggering nanoparticle aggregation. Nanoscale. 2020;12(44):22754-67. doi: 10.1039/d0nr06315k.Wang X., Gong J., Tan W. et al. Adsorption of proteins on oral Zn2+ doped iron oxide nanoparticles in mouse stomach and in vitro: triggering nanoparticle aggregation. Nanoscale. 2020;12(44):22754-67. doi: 10.1039/d0nr06315k.Wu L., Wen W., Wang X. et al. Ultrasmall iron oxide nanoparticles cause significant toxicity by specifically inducing acute oxidative stress to multiple organs. Part Fibre Toxicol. 2022;19:24. doi: 10.1186/s12989-022-00465-y.Wu L., Wen W., Wang X. et al. Ultrasmall iron oxide nanoparticles cause significant toxicity by specifically inducing acute oxidative stress to multiple organs. Part Fibre Toxicol. 2022;19:24. doi: 10.1186/s12989-022-00465-y.Raĭkher Yu.L., Stepanov V.I., Stolyar S.V. et al. Magnetic properties of biomineral particles produced by bacteria Klebsiella oxytoca. Physics of the Solid State. 2010;52:298-305. doi: 10.1134/S1063783410020125.Raĭkher Yu.L., Stepanov V.I., Stolyar S.V. et al. Magnetic properties of biomineral particles produced by bacteria Klebsiella oxytoca. Physics of the Solid State. 2010;52:298-305. doi: 10.1134/S1063783410020125.Vandebriel R.J., Vermeulen J.P., van Engelen L.B. et al. The crystal structure of titanium dioxide nanoparticles influences immune activity in vitro and in vivo. Part Fibre Toxicol. 2018;15:9. doi: 10.1186/s12989-018-0245-5.Vandebriel R.J., Vermeulen J.P., van Engelen L.B. et al. The crystal structure of titanium dioxide nanoparticles influences immune activity in vitro and in vivo. Part Fibre Toxicol. 2018;15:9. doi: 10.1186/s12989-018-0245-5.

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