Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis
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,...
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Belgorod National Research University
2024-09-01
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| Series: | Research Results in Pharmacology |
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| Online Access: | https://rrpharmacology.ru/index.php/journal/article/view/514 |
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| author | Yana V. Loboda Mikhail V. Korokin Alexey V. Kuznetsov Tatiana N. Malorodova Anton P. Danilenko Anna A. Peresypkina Oleg S. Gudyrev Ol’ga A. Kop’eva Tatyana G. Pokrovskaya Liliya V. Korokina Valeriya N. Khruslova Valeriya A. Nazarenko Tatyana V. Avtina Alexey V. Deikin Aleksandr A. Dolzhikov Tatiana V. Puzanova Lyudmila M. Danilenko |
| author_facet | Yana V. Loboda Mikhail V. Korokin Alexey V. Kuznetsov Tatiana N. Malorodova Anton P. Danilenko Anna A. Peresypkina Oleg S. Gudyrev Ol’ga A. Kop’eva Tatyana G. Pokrovskaya Liliya V. Korokina Valeriya N. Khruslova Valeriya A. Nazarenko Tatyana V. Avtina Alexey V. Deikin Aleksandr A. Dolzhikov Tatiana V. Puzanova Lyudmila M. Danilenko |
| author_sort | Yana V. Loboda |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fedb506e6efa4643afd7ba238562b504 |
| institution | Kabale University |
| issn | 2658-381X |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj-art-fedb506e6efa4643afd7ba238562b5042025-01-08T12:41:42ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2024-09-01103859310.18413/rrpharmacology.10.514Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasisYana V. Loboda0https://orcid.org/0009-0004-0237-5233Mikhail V. Korokin1https://orcid.org/0000-0001-5402-0697Alexey V. Kuznetsov2https://orcid.org/0000-0003-1889-1297Tatiana N. Malorodova3https://orcid.org/0000-0002-4186-2577Anton P. Danilenko4https://orcid.org/0009-0001-2419-8109Anna A. Peresypkina5https://orcid.org/0000-0003-2829-9860Oleg S. Gudyrev6https://orcid.org/0000-0003-0097-000XOl’ga A. Kop’eva7https://orcid.org/0009-0008-2505-2946Tatyana G. Pokrovskaya8https://orcid.org/0000-0001-6802-5368Liliya V. Korokina9https://orcid.org/0000-0002-4115-1564Valeriya N. Khruslova10https://orcid.org/0009-0005-4678-6138Valeriya A. Nazarenko11https://orcid.org/0009-0004-5970-8238Tatyana V. Avtina12https://orcid.org/0000-0003-0509-5996Alexey V. Deikin13https://orcid.org/0000-0001-9960-0863Aleksandr A. Dolzhikov14https://orcid.org/0000-0001-7425-8416Tatiana V. Puzanova15https://orcid.org/0009-0003-7926-8447Lyudmila M. Danilenko16https://orcid.org/0000-0001-6101-8712Belgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityIntroduction: 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.https://rrpharmacology.ru/index.php/journal/article/view/514potassium 5-hydroxynicotinatedoxorubicincoefficient stттioxidative stresswistar rats |
| spellingShingle | Yana V. Loboda Mikhail V. Korokin Alexey V. Kuznetsov Tatiana N. Malorodova Anton P. Danilenko Anna A. Peresypkina Oleg S. Gudyrev Ol’ga A. Kop’eva Tatyana G. Pokrovskaya Liliya V. Korokina Valeriya N. Khruslova Valeriya A. Nazarenko Tatyana V. Avtina Alexey V. Deikin Aleksandr A. Dolzhikov Tatiana V. Puzanova Lyudmila M. Danilenko Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis Research Results in Pharmacology potassium 5-hydroxynicotinate doxorubicin coefficient stттi oxidative stress wistar rats |
| title | Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis |
| title_full | Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis |
| title_fullStr | Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis |
| title_full_unstemmed | Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis |
| title_short | Novel derivative of nicotinic acid ameliorates doxorubicin-induced cardiac injury via regulation of redox homeostasis |
| title_sort | novel derivative of nicotinic acid ameliorates doxorubicin induced cardiac injury via regulation of redox homeostasis |
| topic | potassium 5-hydroxynicotinate doxorubicin coefficient stттi oxidative stress wistar rats |
| url | https://rrpharmacology.ru/index.php/journal/article/view/514 |
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