Journal of Evolutionary Biochemistry and PhysiologyJournal of Evolutionary Biochemistry and PhysiologyЖурнал эволюционной биохимии и физиологии0044-45293034-5529The Russian Academy of Sciences64808610.31857/S0044452924030058YXHEASEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticlePathology of doxorubicin-induced organopathies under different intravenous nicotinamide riboside administration modesМорфология доксорубицин-индуцированных органопатий при разных режимах внутривенного введения никотинамид рибозидаPodyachevaE. Yu.ПодъячеваЕ. Ю.
Russian Federation
ekaterinapodyachevaspb@gmail.comSemenovaN. Yu.СеменоваН. Ю.
Russian Federation
ekaterinapodyachevaspb@gmail.comArtyukhinaZ. E.АртюхинаЗ. Е.
Russian Federation
ekaterinapodyachevaspb@gmail.comZinserlingV. A.ЦинзерлингВ. А.
Russian Federation
ekaterinapodyachevaspb@gmail.comToropovaYa. G.ТороповаЯ. Г.
Russian Federation
ekaterinapodyachevaspb@gmail.comAlmazov National Medical Research Centre, Ministry of Health of the Russian FederationНациональный медицинский исследовательский центр имени В.А. Алмазова Минздрава России1505202460326428128012025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0044-4529/article/view/648086

Doxorubicin (DOX) is a potent chemotherapeutic drug, but its clinical use is hindered by significant side effects on vital organs like the heart, kidneys, lungs, liver, and intestines. Currently, there is a lack of effective drugs that can provide simultaneous cardioprotection and organ protection during chemotherapy. Nicotinamide riboside (NR) holds promise as a pharmacological agent capable of offering comprehensive protection against the systemic toxicity caused by DOX. This study aimed to comprehensively evaluate the morphological characteristics of vital organs (heart, lungs, liver, kidneys) in Wistar rats with chronic doxorubicin-induced cardiomyopathy using various intravenous administration modes of NR as a protective agent. Sixty male SPF Wistar rats weighing 283 ± 22 g were divided into four groups: intact, control (DOX administered intraperitoneally), combined mode (the simultaneous use of DOX and NR) and preventive mode (the preliminary use of NR to realize the cumulative effect in cells, and its further joint use together with DOX) intravenous NR administration. Animal observation spanned two months after drug administration, followed by the collection of hearts, lungs, liver, and kidneys for morphological analysis. Echocardiographic assessment confirmed DOX cardiotoxicity. The study revealed that the hearts, kidneys and lungs exhibited more pronounced toxic effects of DOX compared to the liver. Both NR administration modes demonstrated protective effects, with the preventive regime showing the greatest efficacy in safeguarding vital organs.

Доксорубицин (ДОКС) является одним из наиболее эффективных химиотерапевтических препаратов антрациклинового ряда, при этом его применение в клинической практике ограничено наличием ярко выраженных побочных эффектов в отношении жизненно важных органов – сердца, почек, легких, печени. На сегодняшний день отсутствуют эффективные препараты, способные снизить системное токсическое действие ДОКС. Никотинамид рибозид (НР) может рассматриваться в качестве перспективного фармакологического агента, способного обеспечивать комплексный защитный эффект от системного влияния токсических эффектов ДОКС. Целью данной работы являлась комплексная морфологическая оценка жизненно важных органов (сердце, легкие, печень, почки) крыс стока Wistar в условиях воздействия ДОКС при внутривенном введении НР в различных режимах в качестве протективного агента. Работа выполнена на 60 самцах крыс весом 283 ± 22 гр. Животные были разделены на 4 группы: интактная, контрольная (внутрибрюшинное введение ДОКС), опытные группы животных (внутрибрюшинное введение ДОКС) с превентивным и сочетанным режимом внутривенного введения НР. По окончании введения фармакологических агентов наблюдение за животными составило 2 месяца. На этапе окончания исследования у наркотизированных животных осуществляли взятие сердца, легких, печени, почек для проведения морфологических исследований. Эхокардиографический анализ осуществлялся с целью подтверждения развития кардиотоксических эффектов ДОКС. В условиях воздействия ДОКС наибольшие морфологические изменения наблюдались в сердце, почках и легких. Используемые схемы введения НР обеспечивали протективный эффект в отношении жизненно важных органов, при этом наиболее выраженное защитное действие НР наблюдалось при использовании превентивного режима.

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