medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2019-98-10-1161-1165medlit-434Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕPREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATIONОценка токсических эффектов магнитоконтрастирующего диагностического гадолиний-содержащего нанокомпозитаEvaluation of toxic effects of magnetic contrast diagnostic gadolinium-containing nanocompositehttps://orcid.org/0000-0003-1052-4601СоседоваЛариса МихайловнаSosedovaLarisa M.

Доктор мед. наук, проф., зав. лабораторией биомоделирования и трансляционной медицины ФГБНУ ВСИМЭИ.

e-mail: sosedlar@mail.ru

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

sosedlar@mail.ruhttps://orcid.org/0000-0002-0665-8060ТитовЕ. А.TitovE. A.noemail@neicon.ruhttps://orcid.org/0000-0002-6100-6292НовиковМ. А.NovikovM. A.noemail@neicon.ruhttps://orcid.org/0000-0002-8165-8052ВокинаВ. А.VokinaV. A.noemail@neicon.ruhttps://orcid.org/0000-0003-2536-1550РукавишниковВ. С.RukavishnikovV. S.noemail@neicon.ruФедеральное государственное бюджетное научное учреждение «Восточно-Сибирский институт медико-экологических исследований»; Федеральное государственное бюджетное учреждение науки «Иркутский научный центр» Сибирского отделения Российской академии наукEast-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of ScienceФедеральное государственное бюджетное научное учреждение «Восточно-Сибирский институт медико-экологических исследований»East-Siberian Institute of Medical and Ecological Research201914102020981011611165Copyright © Соседова Л.М., Титов Е.А., Новиков М.А., Вокина В.А., Рукавишников В.С., 20202020Соседова Л.М., Титов Е.А., Новиков М.А., Вокина В.А., Рукавишников В.С.Sosedova L.M., Titov E.A., Novikov M.A., Vokina V.A., Rukavishnikov V.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/434Введение

Введение. Для усиления контрастирования и повышения диагностической чувствительности при проведении магнитной резонансной терапии (МРТ) в последние годы используют магнитные наночастицы, способные одновременно оказывать и терапевтическое воздействие на патологический очаг. Последнее осуществляется путём эффективного захвата нейтронов, который среди всех химических элементов наиболее выражен у гадолиния. Применение наночастиц гадолиния, инкапсулированных в полимерную матрицу, позволяет увеличить биодоступность наночастиц, снижает возможную токсичность препаратов.

Цель

Цель. Оценка воздействия новой нанокомпозитной магнитоактивной металлокомплексной гадолиниевой системы на морфофункциональное состояние нервной ткани, печени и почек крыс.

Материал и методы

Материал и методы. Экспериментальные исследования биологических эффектов нанокомпозита гадолиний-арабиногалактан (Gd-АГ) проведены на крысах, которым вводили раствор внутрибрюшинно в течение 10 дней в дозе 500 мкг/кг в 0,5 мл физиологического раствора. Через сутки после окончания экспозиции животных умерщвляли путём декапитации под лёгким эфирным наркозом. Для выполнения патоморфологических исследований фронтальные срезы височно-теменной зоны сенсомоторной коры головного мозга, ткани печени и почек окрашивали на обычных гистологических предметных стёклах гематоксилином и эозином для обзорной микроскопии. Для исследования биологического ответа организма на субклеточном уровне применяли иммуногистохимический метод определения активности белков-модуляторов апоптоза bcl-2, caspase-3 и hsp70 в нейронах головного мозга белых крыс.

Результаты

Результаты. Гистологический анализ тканей выявил выраженную компенсаторную реакцию печени, нарушение функциональной активности почек. Снижение общего числа нормальных нейронов на единицу площади в ткани головного мозга и увеличение числа актов нейронофагии указывает на начальный этап нейродегенеративного процесса. При оценке внутриклеточного метаболизма нейронов не установлено наличия признаков, характерных для апоптотического процесса.

Заключение

Заключение. Оценивая в целом результаты проведённых экспериментов, можно заключить, что подострое воздействие Gd-АГ в дозе 500 мкг/кг вызывает нарушение морфофункционального состояния тканей печени, почек и нервной, а также модуляцию клеточной протеомики.

Introduction

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

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

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

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

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.

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