pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2024-13-3-1730pharmjournal-1913Research ArticleДОКЛИНИЧЕСКИЕ И КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯPRECLINICAL AND CLINICAL STUDIESРоль доксорубицина в формировании кардиотоксичности – консенсусное заявление. Часть II. Кардиотоксичность доксорубицина, не связанная с миоцитами, и стратегия кардиопротекции (обзор)The role of doxorubicin in the formation of cardiotoxicity is a consensus statement. Part II. Cardiotoxicity of doxorubicin unrelated to myocytes and cardioprotection strategy (review)https://orcid.org/0009-0004-5936-827XАндреевД. А.AndreevD. A.

123098, г. Москва, ул. Маршала Новикова, д. 23

23, Marshala Novikova str., Moscow, 123098

https://orcid.org/0000-0001-5545-135XБалакинЕ. И.BalakinE. I.

123098, г. Москва, ул. Маршала Новикова, д. 23

23, Marshala Novikova str., Moscow, 123098

evgbalakin@yandex.ruhttps://orcid.org/0000-0002-9241-7238СамойловА. С.SamoilovA. S.

123098, г. Москва, ул. Маршала Новикова, д. 23

23, Marshala Novikova str., Moscow, 123098

https://orcid.org/0000-0003-3396-5813ПустовойтВ. И.PustovoitV. I.

123098, г. Москва, ул. Маршала Новикова, д. 23

23, Marshala Novikova str., Moscow, 123098

Федеральное государственное бюджетное учреждение «Государственный научный центр Федеральный медицинский биофизический центр им. А. И. Бурназяна ФМБА России»РоссияState Research Center – A. I. Burnasyan Federal Medical Biophysical Center of Federal Medical Biological AgencyRussian Federation202426082024133208218Copyright © Андреев Д.А., Балакин Е.И., Самойлов А.С., Пустовойт В.И., 20242024Андреев Д.А., Балакин Е.И., Самойлов А.С., Пустовойт В.И.Andreev D.A., Balakin E.I., Samoilov A.S., Pustovoit V.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/1913Введение

Введение. Применение доксорубицина в клинической практике сопровождается кумулятивным и дозозависимым токсическим воздействием на кардиомиоциты, приводящим к увеличению риска смертности среди пациентов с онкологическими заболеваниями и, как следствие, возникновению ограничений в отношении его применения.

Текст

Текст. Опасной нежелательной реакцией доксорубицина является кардиомиопатия, приводящая к застойной сердечной недостаточности. В основе кардиотоксичности лежат как минимум несколько патофизиологических механизмов (детальнее описанных в первой части обзора), приводящих к повреждению кардиомиоцитов в результате окислительного стресса с образованием свободных радикалов, нарушения функции митохондрий, аутофагии, высвобождения оксида азота и медиаторов воспаления, а также изменения экспрессии генов и белков, что приводит к апоптозу. В текущей (второй) части обзора представлена подробная информация о современном понимании патофизиологических механизмов, лежащих в основе уже описанной кардиотоксичности, и влияния доксорубицина на другие клетки сердца. Использование кардиопротективных стратегий позволит снизить выраженность и вероятность развития кардиотоксичности. В данной статье описаны стратегии, основанные на снижении максимальной кумулятивной дозы, изменении характера введения доксорубицина, использовании пегилированных липосомальных форм и кардиопротекстивных средств, а также физических нагрузок.

Заключение

Заключение. Несмотря на огромное количество научных работ, посвященных различным аспектам кардиотоксичности доксорубицина, ее профилактики и лечения, данный вопрос требует более тщательного изучения и выработки более совершенных методов ранней диагностики, профилактики и более эффективной терапии этого осложнения.

Introduction

Introduction. The use of doxorubicin in clinical practice has shown cumulative and dose-dependent toxic effects on cardiomyocytes, leading to an increase of mortality risk among patients with cancer and as a resulting to restrictions in the indications for its use.

Text

Text. A dangerous adverse reaction of doxorubicin is cardiomyopathy, leading to congestive heart failure. Cardiotoxicity is based on at least several pathophysiological mechanisms (described in more detail in the first part of the review), leading to damage to cardiomyocytes as a result of oxidative stress with the formation of free radicals, dysfunction of mitochondria, autophagy, release of nitric oxide and inflammatory mediators, as well as changes in gene expression and proteins leading to apoptosis. The current (second) part of the review provides detailed information on the actual understanding of the pathophysiological mechanisms underlying the described cardiotoxicity, the effect of doxorubicin on other heart cells. The use of cardioprotective strategies will reduce the severity and likelihood of developing cardiotoxicity. This article describes strategies based on reducing the maximum cumulative dose, changing the speed of doxorubicin administration, using pegylated liposomal formulations and cardioprotective agents, as well as exercise.

Conclusion

Conclusion. Despite the huge number of scientific papers devoted to various aspects of cardiotoxicity of doxorubicin, its prevention and treatment, this issue requires more careful study and development of more advanced methods of early diagnosis, prevention and more effective therapy the complication.

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