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

Authors

DOI:

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

Abstract

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 StTTI 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 StТТI 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.

Graphical Abstract

Keywords:

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

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Author Contribution

Yana V. Loboda, Belgorod State National Research University

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.

Mikhail V. Korokin, Belgorod State National Research University

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.

Alexey V. Kuznetsov, Belgorod State National Research University

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.

Tatiana N. Malorodova, Belgorod State National Research University

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.

Anton P. Danilenko, Belgorod State National Research University

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.

Anna A. Peresypkina, Belgorod State National Research University,

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.

Oleg S. Gudyrev, Belgorod State National Research University

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.

Ol’ga A. Kop’eva, Belgorod State National Research University

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.

Tatyana G. Pokrovskaya, Belgorod State National Research University

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.

Liliya V. Korokina, Belgorod State National Research University

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.

Valeriya N. Khruslova, Belgorod State National Research University

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.

Valeriya A. Nazarenko, Belgorod State National Research University

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.

Tatyana V. Avtina, Belgorod State National Research University

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.

Alexey V. Deikin, Belgorod State National Research University

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.

Aleksandr A. Dolzhikov, Belgorod State National Research University

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.

Tatiana V. Puzanova, Belgorod State National Research University

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.

Lyudmila M. Danilenko, Belgorod State National Research University

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.

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Published

30-09-2024

How to Cite

Loboda YV, Korokin MV, Kuznetsov AV, Malorodova TN, Danilenko AP, Peresypkina AA, Gudyrev OS, Kop’eva OA, Pokrovskaya TG, Korokina LV, Khruslova VN, Nazarenko VA, Avtina TV, Deikin AV, Dolzhikov AA, Puzanova TV, Danilenko LM (2024) Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis. Research Results in Pharmacology 10(3): 85–93. https://doi.org/10.18413/rrpharmacology.10.514

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Experimental Pharmacology

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