morphoМорфологические ведомостиMorphological newsletter1812-31712686-8741Private Medical University REAVIZ10.20340/mv-mn.2024.32(1).845morpho-845Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯRESEARCH ARTICLESМОРФОЛОГИЧЕСКИЕ РЕАКЦИИ МИОКАРДА И ПЕЧЕНИ МЫШЕЙ CD-1 НА ВВЕДЕНИЕ РАЗЛИЧНЫХ ДОЗ БОРФЕНИЛАЛАНИНАTHE CD-1 MICE MYOCARDIUM AND LIVER MORPHOLOGICAL REACTIONS AT THE TREATMENT BY DIFFERENT DOSES OF BORPHENYLALANINEhttps://orcid.org/0000-0002-9220-8663КаныгинВладимир ВладимировичKanyginVladimir V.

кандидат медицинских наук, доцент, старший научный сотрудник Института ядерной физики имени Г.И. Будкера Сибирского отделения РАН; заведующий лабораторией ядерной и инновационной медицины, доцент кафедры физики элементарных частиц Новосибирского национального исследовательского государственного университета

Candidate of Medical Sciences, Docent, Senior Researcher of the Budker Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences; Head of the Laboratory of Nuclear and Innovative Medicine and Associate Professor of the Department of Elementary Particle Physics of the Novosibirsk National Research State University

kanigin@mail.ruhttps://orcid.org/0000-0002-9480-8814КолдышеваЕлена ВладимировнаKoldyshevaElena V.

доктор биологических наук, главный научный сотрудник, руководитель лаборатории молекулярных механизмов патологических процессов Института молекулярной патологии и патоморфологии, Федеральный исследовательский центр фундаментальной и трансляционной медицины (ФИЦ ФТМ). Старший научный сотрудник лаборатории ядерной и инновационной медицины, Новосибирский национальный исследовательский государственный университет

Doctor of Biological Sciences, Chief Researcher, Head of the Laboratory of Molecular Mechanisms of Pathological Processes of the Institute of Molecular Pathology and Pathomorphology of the Federal Research Center for Fundamental and Translational Medicine; Senior Researcher of the Laboratory of Nuclear and Innovative Medicine of the Novosibirsk National Research State University

130066@mail.ruhttps://orcid.org/0000-0002-9412-3874ЗавьяловЕвгений ЛеонидовичZav'yalovEvgeny L.

кандидат биологических наук, заведующий Центром доклинических испытаний SPF-вивария Института цитологии и генетики Сибирского отделения РАН; научный сотрудник лаборатории ядерной и инновационной медицины Новосибирского национального исследовательского государственного университета

Candidate of Biological Sciences, Head of the SPF-Vivarium of the Center for Preclinical Trials of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Researcher of the Laboratory of Nuclear and Innovative Medicine of the Novosibirsk National Research State University

zavjalov@bionet.nsc.ruhttps://orcid.org/0000-0002-8218-2690СоловьеваОльга ИгоревнаSolovyovaOl'ga I.

магистр биологии, младший научный сотрудник Центра доклинических испытаний SPF-вивария Института цитологии и генетики Сибирского отделения РАН; научный сотрудник лаборатории ядерной и инновационной медицины Новосибирского национального исследовательского государственного университета

Master of Biology, Junior Researcher of the SPF-Vivariums of the Center for Preclinical Trials of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Researcher of the Laboratory of Nuclear and Innovative Medicine of the Novosibirsk National Research State University

solovieva@bionet.nsc.ruhttps://orcid.org/0009-0009-3427-9672ПрохороваЕлизавета СергеевнаProkhorovaElizaveta S.

лаборант Центра доклинических испытаний SPF-вивария

Laboratory Assistant of the SPF-Vivariums of the Center for Preclinical Trials

prokhorovaES@bionet.nsc.ruhttps://orcid.org/0000-0003-1109-9985КаныгинНиколай ВладимировичKanyginNikolay V.

студент, лаборант лаборатории ядерной и инновационной медицины

Student, Laboratory Assistant of the Laboratory of Nuclear and Innovative Medicine

kanygin_kolya@mail.ruhttps://orcid.org/0000-0001-6512-1629КапустинаВалентина ИльиничнаKapustinaValentina I.

кандидат биологических наук, старший научный сотрудник лаборатории клинической морфологии важнейших заболеваний Института молекулярной патологии и патоморфологии

Candidate of Biological Sciences, Senior Researcher of the Laboratory of Clinical Morphology of the Most Important Diseases of the Institute of Molecular and General Pathology

kapustina_val@mail.ruИнститут ядерной физики имени Г.И. Будкера Сибирского отделения РАН, Новосибирский национальный исследовательский государственный университет, НовосибирскРоссияBudker Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk National Research State University, NovosibirskRussian FederationФедеральный исследовательский центр фундаментальной и трансляционной медицины, Новосибирский национальный исследовательский государственный университет, НовосибирскРоссияFederal Research Center of the Fundamental and Translational Medicine, Novosibirsk National Research State University, NovosibirskRussian FederationИнститут цитологии и генетики Сибирского отделения РАН, Новосибирский национальный исследовательский государственный университет, НовосибирскРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk National Research State University, NovosibirskRussian FederationИнститут цитологии и генетики Сибирского отделения РАН, Новосибирский национальный исследовательский государственный университет, НовосибирскРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, National Research State University, NovosibirskRussian FederationИнститут цитологии и генетики Сибирского отделения РАН, НовосибирскРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, NovosibirskRussian FederationНовосибирский национальный исследовательский государственный университет, НовосибирскРоссияNovosibirsk National Research State University, NovosibirskRussian FederationФедеральный исследовательский центр фундаментальной и трансляционной медицины, НовосибирскРоссияFederal Research Center of the Fundamental and Translational Medicine, NovosibirskRussian Federation202420062024321ID-845Copyright © Каныгин В.В., Колдышева Е.В., Завьялов Е.Л., Соловьева О.И., Прохорова Е.С., Каныгин Н.В., Капустина В.И., 20242024Каныгин В.В., Колдышева Е.В., Завьялов Е.Л., Соловьева О.И., Прохорова Е.С., Каныгин Н.В., Капустина В.И.Kanygin V.V., Koldysheva E.V., Zav'yalov E.L., Solovyova O.I., Prokhorova E.S., Kanygin N.V., Kapustina V.I.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/845

Перспектива применения бор-нейтронозахватной терапии обусловлена эффективностью метода в отношении радиорезистентных и других видов опухолей, плохо поддающихся традиционным методам лечения или при невозможности их применения. Повышение эффективности терапии требует увеличения дозы вещества, в связи с чем возникает вопрос о его влиянии на условно здоровые ткани. Цель исследования – изучить динамику морфологических изменений в миокарде и печени у мышей после однократной инъекции L-p-бор-фенилаланина в терапевтической и сублетальной дозах. Проведено светооптическое и поляризационно-микроскопическое исследование миокарда и печени мышей-самцов линии CD-1 (n=54) после введения борсодержащего вещества (в дозах 700 и 3000 мг/кг; однократно, внутрибрюшинно), применяемого в клинической бор-нейтронозахватной терапии. Оценка структурных изменений в миокарде и печени проводилась через 1, 3 и 7 суток после введения препарата. Установлено, что введение высоких доз вещества вызывало литические, а в более поздние сроки контрактурные повреждения кардиомиоцитов. Гемодинамические нарушения в виде умеренного полнокровия наблюдались на протяжении всего срока исследования. В печени, независимо от дозы получаемого вещества с 3 суток наблюдались моноцеллюлярные некрозы, инфильтрированные мононуклеарами, что сохранялось до конца эксперимента. Перицентральные гепатоциты часто были в состоянии дистрофии. Независимо от дозы через 1 и 7 суток количество двуядерных гепатоцитов было выше на 14-16% по сравнению с контролем, тогда как на 3 сутки наблюдалось достоверное транзиторное снижение количества двуядерных гепатоцитов, как по сравнению с контролем, так с показателями в другие сроки эксперимент. Наиболее значимые различия наблюдались в группе животных с введением более низкой дозы. Полученные данные свидетельствуют о том, что использованные дозы L-p-бор-фенилаланина при однократном введении вызывают неспецифические структурные изменения миокарда и печени различной степени выраженности, характеризующиеся дозо- и время-зависимым эффектом и требуют изучения в более поздние периоды после введения.

The potential of Boron-neutron capture therapy is driven by its effectiveness for radio-resistant and other types of tumors that are tough to treat with conventional treatments or if they are not available. In order to improve the effectiveness of therapy, the dose of the substance needs to increase, which raises the question of its effect on conventionally healthy tissues. The study is to evaluate the dynamic changes in myocardium and liver in mice caused by a single injection of L-p-boron-phenylalanine, whether it is a therapeutic or sub-lethal dose. The light-optical and polarization microscopic examination of the myocardium and liver of the male mice of the CD-1 (n=54) line was carried out after the injection of the Boron-containing substance (in doses of 700 and 3000 mg/kg; once intraperitoneal) used in clinical Boron-neutron treatment. Evaluation of structural changes in the myocardium and liver was done 1, 3, and 7 days after injection. Cardiomyocytes are susceptible to lytic and contracture damage caused by high doses of the substance. Moderate blood-fullness was observed throughout the study as evidence of hemodynamic impairments. Mononuclear cells infiltrating the liver for 3 days resulted in mono-cellular necrosis, which persisted until the end of the experiment regardless of the dose. Paracentral hepatocytes have been often dystrophic. Regardless of the dose after 1 or 7 days, the number of bi-nuclear hepatocytes was 14-16% higher than the number of control group animals, while for 3 days there was a reliable transient decrease in the number of bi-nuclear hepatocytes both compared to the control group animals and data in other periods of the experiment. The most significant differences were observed in the animal group with the injection of a lower dose. The obtained data show that the used doses of L-p-boron-phenylalanine with a single injection cause non-specific structural changes of the myocardium and liver of varying severity, characterized by dose and time-dependent effects and require study in later periods after substance injection.

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