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l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress
Trazodone (TRZ) is an antidepressant drug which widely used to treat insomnia, but it has a cardiotoxic effect which considered one of the TRZ limitations. The aim of this study was to investigate the protective role of l-carnitine in rats against TRZ-induced cardiotoxicity, as well as to look into...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381465/ https://www.ncbi.nlm.nih.gov/pubmed/35781619 http://dx.doi.org/10.1007/s12012-022-09759-1 |
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author | Khedr, Naglaa F. El-Feky, Ola A. Werida, Rehab H. |
author_facet | Khedr, Naglaa F. El-Feky, Ola A. Werida, Rehab H. |
author_sort | Khedr, Naglaa F. |
collection | PubMed |
description | Trazodone (TRZ) is an antidepressant drug which widely used to treat insomnia, but it has a cardiotoxic effect which considered one of the TRZ limitations. The aim of this study was to investigate the protective role of l-carnitine in rats against TRZ-induced cardiotoxicity, as well as to look into the molecular mechanisms underlying its cardioprotective effects via autophagy-mediated cell death and oxidative stress. Male albino rats were randomized into four experimental groups (n = 8): normal control, TRZ group (TRZ, 20 mg/kg/day), l-carnitine group (LC, 200 mg/kg/day), and Co-treated group (l-carnitine and TRZ). All treatments were administered via oral gavage for 4 weeks. Cardiac enzymes (AST & CK-MB) and serum cardiac troponin T(cTnI) were assessed. Oxidative stress biomarkers in heart tissue (malondialdehyde; MDA, total thiol, and catalase activity) were measured. Autophagy related-genes (ATG-5 and Beclin-1), P62, and TNF-α were quantified. AST and CK-MB and cTnI significantly (p < 0.001) were increased with enhanced autophagy as well as severe histopathological changes which were manifested as scattered chronic inflammatory cells with focal fragmentation of myocardial fibers and loss of nuclei in TRZ-treated group. However, daily administration of l-carnitine (200 mg/kg) for 28 days completely reversed TRZ-induced the increased cardiac enzymes, autophagy, and myocardial inflammatory processes to the normal values. TRZ administration might have the potential to cause cardiotoxic effects that can be treated with l-carnitine administration. |
format | Online Article Text |
id | pubmed-9381465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-93814652022-08-18 l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress Khedr, Naglaa F. El-Feky, Ola A. Werida, Rehab H. Cardiovasc Toxicol Article Trazodone (TRZ) is an antidepressant drug which widely used to treat insomnia, but it has a cardiotoxic effect which considered one of the TRZ limitations. The aim of this study was to investigate the protective role of l-carnitine in rats against TRZ-induced cardiotoxicity, as well as to look into the molecular mechanisms underlying its cardioprotective effects via autophagy-mediated cell death and oxidative stress. Male albino rats were randomized into four experimental groups (n = 8): normal control, TRZ group (TRZ, 20 mg/kg/day), l-carnitine group (LC, 200 mg/kg/day), and Co-treated group (l-carnitine and TRZ). All treatments were administered via oral gavage for 4 weeks. Cardiac enzymes (AST & CK-MB) and serum cardiac troponin T(cTnI) were assessed. Oxidative stress biomarkers in heart tissue (malondialdehyde; MDA, total thiol, and catalase activity) were measured. Autophagy related-genes (ATG-5 and Beclin-1), P62, and TNF-α were quantified. AST and CK-MB and cTnI significantly (p < 0.001) were increased with enhanced autophagy as well as severe histopathological changes which were manifested as scattered chronic inflammatory cells with focal fragmentation of myocardial fibers and loss of nuclei in TRZ-treated group. However, daily administration of l-carnitine (200 mg/kg) for 28 days completely reversed TRZ-induced the increased cardiac enzymes, autophagy, and myocardial inflammatory processes to the normal values. TRZ administration might have the potential to cause cardiotoxic effects that can be treated with l-carnitine administration. Springer US 2022-07-04 2022 /pmc/articles/PMC9381465/ /pubmed/35781619 http://dx.doi.org/10.1007/s12012-022-09759-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Khedr, Naglaa F. El-Feky, Ola A. Werida, Rehab H. l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress |
title | l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress |
title_full | l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress |
title_fullStr | l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress |
title_full_unstemmed | l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress |
title_short | l-Carnitine Mitigates Trazadone Induced Rat Cardiotoxicity Mediated via Modulation of Autophagy and Oxidative Stress |
title_sort | l-carnitine mitigates trazadone induced rat cardiotoxicity mediated via modulation of autophagy and oxidative stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381465/ https://www.ncbi.nlm.nih.gov/pubmed/35781619 http://dx.doi.org/10.1007/s12012-022-09759-1 |
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