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Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway
Doxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with uniqu...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291064/ https://www.ncbi.nlm.nih.gov/pubmed/37377932 http://dx.doi.org/10.3389/fphar.2023.1206782 |
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author | Al-Kenany, Sara A. Al-Shawi, Nada N. |
author_facet | Al-Kenany, Sara A. Al-Shawi, Nada N. |
author_sort | Al-Kenany, Sara A. |
collection | PubMed |
description | Doxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with unique antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of cafestol on DOX-induced cardiotoxicity in rats. Wistar albino rats of both sexes were administered cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to induce toxicity. The result showed that Caf significantly improved cardiac injury induced by doxorubicin, decreased serum levels of CK-MB, LDH, ALP, and ALT, and improved histopathological changes. In addition, cafestol significantly inhibited DOX-induced cardiac oxidative stress as seen in the reduced level of MDA and increased GSH, SOD, CAT, and Gpx-1 cardiac tissue levels; cafestol significantly enhanced Nrf2 gene and protein expression and promoted the expression of downstream antioxidant genes HO-1 and NQO-1 and downregulated Keap1 and NF-κB genes’ expression; in addition, Caf significantly reduced inflammatory mediators, TNF-α, and IL-1β levels and inhibited cardiac apoptosis by modulating Bax and Casp 3 tissue levels and reduced TUNEL-positive cardiomyocytes. In conclusion, the present study confirmed that cafestol improved the cardiotoxic effects induced by doxorubicin through the regulation of apoptosis and oxidative stress response through the Nrf2 pathway; this study suggests that cafestol may serve as a potential adjuvant in chemotherapy to alleviate DOX-induced toxicities. |
format | Online Article Text |
id | pubmed-10291064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102910642023-06-27 Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway Al-Kenany, Sara A. Al-Shawi, Nada N. Front Pharmacol Pharmacology Doxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with unique antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of cafestol on DOX-induced cardiotoxicity in rats. Wistar albino rats of both sexes were administered cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to induce toxicity. The result showed that Caf significantly improved cardiac injury induced by doxorubicin, decreased serum levels of CK-MB, LDH, ALP, and ALT, and improved histopathological changes. In addition, cafestol significantly inhibited DOX-induced cardiac oxidative stress as seen in the reduced level of MDA and increased GSH, SOD, CAT, and Gpx-1 cardiac tissue levels; cafestol significantly enhanced Nrf2 gene and protein expression and promoted the expression of downstream antioxidant genes HO-1 and NQO-1 and downregulated Keap1 and NF-κB genes’ expression; in addition, Caf significantly reduced inflammatory mediators, TNF-α, and IL-1β levels and inhibited cardiac apoptosis by modulating Bax and Casp 3 tissue levels and reduced TUNEL-positive cardiomyocytes. In conclusion, the present study confirmed that cafestol improved the cardiotoxic effects induced by doxorubicin through the regulation of apoptosis and oxidative stress response through the Nrf2 pathway; this study suggests that cafestol may serve as a potential adjuvant in chemotherapy to alleviate DOX-induced toxicities. Frontiers Media S.A. 2023-06-12 /pmc/articles/PMC10291064/ /pubmed/37377932 http://dx.doi.org/10.3389/fphar.2023.1206782 Text en Copyright © 2023 Al-Kenany and Al-Shawi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Al-Kenany, Sara A. Al-Shawi, Nada N. Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway |
title | Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway |
title_full | Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway |
title_fullStr | Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway |
title_full_unstemmed | Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway |
title_short | Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway |
title_sort | protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the nrf2 pathway |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291064/ https://www.ncbi.nlm.nih.gov/pubmed/37377932 http://dx.doi.org/10.3389/fphar.2023.1206782 |
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