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Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis

BACKGROUND: Doxorubicin (DOX) is commonly used in the treatment of many types of cancers but its cardiotoxicity is limiting its clinical use. Beyond its anticoagulant action, enoxaparin (ENX), a low molecular weight heparin, has been shown to exert multiple pharmacological actions including antioxid...

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Autores principales: Shaker, Reem Ali, Abboud, Samer Hassan, Assad, Hayder Chasib, Hadi, Najah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763526/
https://www.ncbi.nlm.nih.gov/pubmed/29321061
http://dx.doi.org/10.1186/s40360-017-0184-z
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author Shaker, Reem Ali
Abboud, Samer Hassan
Assad, Hayder Chasib
Hadi, Najah
author_facet Shaker, Reem Ali
Abboud, Samer Hassan
Assad, Hayder Chasib
Hadi, Najah
author_sort Shaker, Reem Ali
collection PubMed
description BACKGROUND: Doxorubicin (DOX) is commonly used in the treatment of many types of cancers but its cardiotoxicity is limiting its clinical use. Beyond its anticoagulant action, enoxaparin (ENX), a low molecular weight heparin, has been shown to exert multiple pharmacological actions including antioxidant, anti-inflammatory and antiapoptotic effects. Therefore, the current study aimed to assess if ENX could ameliorate cardiotoxicity induced by DOX. METHODS: Twenty-one adult male Wistar albino rats were randomly allocated into three groups (n = 7 each) of control, receiving 0.9% saline (i.p.), DOX, receiving 2.5 mg/kg of DOX (i.p.) thrice weekly; and DOX + ENX, receiving ENX (250 IU/kg/day i.p.) and a DOX dose equivalent to that of the DOX only group. RESULTS: DOX-induced cardiotoxicity was indicated by marked increases in cardiac troponin I (cTnI) and severe histological lesions, which significantly correlated with cardiotoxicity, oxidative stress, inflammation and apoptosis markers, compared to controls. DOX group also showed elevations in malondialdehyde (MDA), a marker of oxidative stress, and reductions in total antioxidant capacity (TAC). Cardiac inflammatory markers including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and caspase-3, an apoptotic marker, were also elevated in the DOX group. DOX, however, did not significantly alter brain natriuretic peptide (BNP) levels. ENX significantly attenuated, but not completely reversed, DOX-induced cardiotoxicity through lowering cTnI and improving cardiomyopathy histopathological scores as compared to the DOX group. ENX also decreased MDA, increased TAC of rats’ heart to levels relatively comparable to control. Significant reductions in TNF-α, IL-1β and caspase-3 were also observed following ENX treatment relative to the DOX only group. CONCLUSIONS: Collectively, these results describe a cardioprotective effect for ENX against DOX-induced cardiotoxicity which is likely facilitated via suppression of oxidative stress, inflammation and apoptosis.
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spelling pubmed-57635262018-01-17 Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis Shaker, Reem Ali Abboud, Samer Hassan Assad, Hayder Chasib Hadi, Najah BMC Pharmacol Toxicol Research Article BACKGROUND: Doxorubicin (DOX) is commonly used in the treatment of many types of cancers but its cardiotoxicity is limiting its clinical use. Beyond its anticoagulant action, enoxaparin (ENX), a low molecular weight heparin, has been shown to exert multiple pharmacological actions including antioxidant, anti-inflammatory and antiapoptotic effects. Therefore, the current study aimed to assess if ENX could ameliorate cardiotoxicity induced by DOX. METHODS: Twenty-one adult male Wistar albino rats were randomly allocated into three groups (n = 7 each) of control, receiving 0.9% saline (i.p.), DOX, receiving 2.5 mg/kg of DOX (i.p.) thrice weekly; and DOX + ENX, receiving ENX (250 IU/kg/day i.p.) and a DOX dose equivalent to that of the DOX only group. RESULTS: DOX-induced cardiotoxicity was indicated by marked increases in cardiac troponin I (cTnI) and severe histological lesions, which significantly correlated with cardiotoxicity, oxidative stress, inflammation and apoptosis markers, compared to controls. DOX group also showed elevations in malondialdehyde (MDA), a marker of oxidative stress, and reductions in total antioxidant capacity (TAC). Cardiac inflammatory markers including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and caspase-3, an apoptotic marker, were also elevated in the DOX group. DOX, however, did not significantly alter brain natriuretic peptide (BNP) levels. ENX significantly attenuated, but not completely reversed, DOX-induced cardiotoxicity through lowering cTnI and improving cardiomyopathy histopathological scores as compared to the DOX group. ENX also decreased MDA, increased TAC of rats’ heart to levels relatively comparable to control. Significant reductions in TNF-α, IL-1β and caspase-3 were also observed following ENX treatment relative to the DOX only group. CONCLUSIONS: Collectively, these results describe a cardioprotective effect for ENX against DOX-induced cardiotoxicity which is likely facilitated via suppression of oxidative stress, inflammation and apoptosis. BioMed Central 2018-01-10 /pmc/articles/PMC5763526/ /pubmed/29321061 http://dx.doi.org/10.1186/s40360-017-0184-z Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Shaker, Reem Ali
Abboud, Samer Hassan
Assad, Hayder Chasib
Hadi, Najah
Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis
title Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis
title_full Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis
title_fullStr Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis
title_full_unstemmed Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis
title_short Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis
title_sort enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763526/
https://www.ncbi.nlm.nih.gov/pubmed/29321061
http://dx.doi.org/10.1186/s40360-017-0184-z
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