Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis

Яна В. Лобода; Михаил В. Корокин; Алексей В. Кузнецов; Татьяна Н. Малородова; Антон П. Даниленко; Анна А. Пересыпкина; Олег С. Гудырев; Ольга А. Копьева; Татьяна Г. Покровская; Лилия В. Корокина; Валерия Н. Хруслова; Валерия А. Назаренко; Татьяна В. Автина; Алексей В. Дейкин; Александр А. Должиков; Татьяна В. Пузанова; Людмила М. Даниленко

doi:10.18413/rrpharmacology.10.514

Авторы

Яна В. Лобода Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0004-0237-5233
Михаил В. Корокин Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0001-5402-0697
Алексей В. Кузнецов Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-1889-1297
Татьяна Н. Малородова Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0002-4186-2577
Антон П. Даниленко Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0001-2419-8109
Анна А. Пересыпкина Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-2829-9860
Олег С. Гудырев Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-0097-000X
Ольга А. Копьева Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0008-2505-2946
Татьяна Г. Покровская Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0001-6802-5368
Лилия В. Корокина Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0002-4115-1564
Валерия Н. Хруслова Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0005-4678-6138
Валерия А. Назаренко Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0004-5970-8238
Татьяна В. Автина Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0003-0509-5996
Алексей В. Дейкин Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0001-9960-0863
Александр А. Должиков Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0001-7425-8416
Татьяна В. Пузанова Белгородский государственный национальный исследовательский университет https://orcid.org/0009-0003-7926-8447
Людмила М. Даниленко Белгородский государственный национальный исследовательский университет https://orcid.org/0000-0001-6101-8712

DOI:

https://doi.org/10.18413/rrpharmacology.10.514

Аннотация

Introduction: Doxorubicin (DOX) is an anthracycline antibiotic with considerable significance in clinics as an anticancer agent, which is limited by its cardiotoxicity, though. A large number of possible therapeutic strategies for reducing cardiotoxicity with doxorubicin have been studied. However, none of them fully meets the requirements of clinical practice. The aim of the study: to evaluate the cardioprotective effects of a new original heterocyclic compound, a pyridine-3-carboxylic acid derivative potassium 5-hydroxynicotinate.

Materials and Methods: Cardiac injury was induced by intraperitoneal administration of doxorubicin (DOX) at a dose of 20 mg/kg. After 48 hours, the parameters of left ventricular contractility and S_tTTI coefficient were assessed on isolated heart in the Langendorff system under the conditions of 480 beats per minute for 11 seconds. Additionally, specific markers of myocardial injury were determined. The lipid peroxidation products and SOD activity were measured as well to challenge whether the compound is able to reduce oxidative stress.

Results: The study showed that pretreatment by potassium 5-hydroxynicotinate (35 mg/kg, 48 h) attenuated DOX-induced damage, resulting in a significant decrease in the S_t_ТТ_I coefficient to 3.3 values and in the restoration of the antioxidant activity of enzymes.

Conclusion: The obtained data totally demonstrate the protective effects of potassium 5-hydroxynicotinate in DOX-induced cardiomyopathy. A significant role in potassium 5-hydroxynicotinate-mediated cardioprotection is, apparently, related to the reduction of oxidative stress and down-regulation of the level of intracellular calcium.

Графическая аннотация

Ключевые слова:

potassium 5-hydroxynicotinate, doxorubicin, coefficient StТТI, oxidative stress, Wistar rats

Библиографические ссылки

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Вклад авторов

Яна В. Лобода, Белгородский государственный национальный исследовательский университет

MD, postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: loboda.yana0104@yandex.ru; ORCID ID: https://orcid.org/0009-0004-0237-5233. The author took part in conceptualization and direction development of the research, generation of key aims and objectives conducting experimental work, analysing the material, and writing the text of the article.

Михаил В. Корокин, Белгородский государственный национальный исследовательский университет

Mikhail V. Korokin, Doct. Sci. (Medicine), Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: mkorokin@mail.ru, ORCID ID:https://orcid.org/0000-0001-5402-0697. The author took part in direction development of the research and in the analysis of the material.

Алексей В. Кузнецов, Белгородский государственный национальный исследовательский университет

Postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: kav8080@bk.ru; ORCID ID: https://orcid.org/0000-0003-1889-1297. The author took part in the experimental work and biochemical research.

Татьяна Н. Малородова, Белгородский государственный национальный исследовательский университет

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: malorodova_tn@mail.ru; ORCID ID: https://orcid.org/0000-0002-4186-2577. The author made a contribution to collection, analysis and interpretation of the data for the paper.

Антон П. Даниленко, Белгородский государственный национальный исследовательский университет

Postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: 1190540@bsu.edu.ru; ORCID ID: https://orcid.org/0009-0001-2419-8109. The author took part in the experimental work.

Анна А. Пересыпкина, Белгородский государственный национальный исследовательский университет

Doct. Sci. (Biology), Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: peresypkina_a@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0003-2829-9860. The author consulted on the research idea and design of the study, and edited the text of the article.

Олег С. Гудырев, Белгородский государственный национальный исследовательский университет

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: gudyrev@mail.ru; ORCID ID: https://orcid.org/0000-0003-0097-000X. The author took part in processing the results obtained.

Ольга А. Копьева, Белгородский государственный национальный исследовательский университет

Medical student, Belgorod State National Research University, Belgorod, Russia; e-mail: o.kopeva@bk.ru; ORCID ID: https://orcid.org/0009-0008-2505-2946. The author took part in enzyme-linked immunosorbent assay.

Татьяна Г. Покровская, Белгородский государственный национальный исследовательский университет

Doct. Sci. (Medicine), Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: pokrovskaia-tg@mail.ru; ORCID ID: https://orcid.org/0000-0001-6802-5368. The author took part in writing the article and processing the results obtained.

Лилия В. Корокина, Белгородский государственный национальный исследовательский университет

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: korokina@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0002-4115-1564. The author was engaged in conducting the literature analysis.

Валерия Н. Хруслова, Белгородский государственный национальный исследовательский университет

Medical student, Belgorod State National Research University, Belgorod Russia; e-mail: 1212334@bsu.edu.ru; ORCID ID: https://orcid.org/0009-0005-4678-6138. The author took part in search for and analysis of literature on the topic of research; participation in research design, as well as in the implementation of cardiomyopathy.

Валерия А. Назаренко, Белгородский государственный национальный исследовательский университет

Medical student, Belgorod State National Research University, Belgorod, Russia; e-mail: 1212402@bsu.edu.ru; ORCID ID: https://orcid.org/0009-0004-5970-8238. The author was engaged in structuring the article and arranging the references.

Татьяна В. Автина, Белгородский государственный национальный исследовательский университет

PhD in Pharmaceutical Sciences, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: tatyanavtina@yandex.ru; ORCID ID:https://orcid.org/0000-0003-0509-5996. The author made a contribution to collection, analysis and interpretation of the data for the paper.

Алексей В. Дейкин, Белгородский государственный национальный исследовательский университет

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: deykin@bsu.edu.ru; ORCID ID: https://orcid.org/000-0001-9960-0863. The author made a contribution to collection, analysis and interpretation of the data for the paper.

Александр А. Должиков, Белгородский государственный национальный исследовательский университет

Doct. Sci. (Medicine), Professor, Professor of the Department of Human Anatomy and Histology, Belgorod State National Research University, Belgorod, Russia; e-mail: dolzhikov@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0001-7425-8416. The author took part in conceptualization and direction development of the research, and interpretation of the data for the paper.

Татьяна В. Пузанова, Белгородский государственный национальный исследовательский университет

Postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: tatius_ktv@mail.ru; ORCID ID: https://orcid.org/0009-0003-7926-8447. The author participated in the article writing.

Людмила М. Даниленко, Белгородский государственный национальный исследовательский университет

Doct. Sci. (Pharmacy), Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: Danilenko_L@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0001-6101-8712. The author was engaged in collection and interpretation of the data for the paper.