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Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways

Gefitinib is an effective treatment for patients with locally advanced non-small cell lung cancer. However, it is associated with cardiotoxicity that can limit its clinical use. Liraglutide, a glucagon-like peptide 1 receptor agonist, showed potent cardioprotective effects with the mechanism is yet...

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Autores principales: AlAsmari, Abdullah F., Ali, Nemat, AlAsmari, Fawaz, AlAnazi, Wael A., AlShammari, Musaad A., Al-Harbi, Naif O., Alhoshani, Ali, As Sobeai, Homood M., AlSwayyed, Mohammed, AlAnazi, Mohammed M., AlGhamdi, Nader S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132601/
https://www.ncbi.nlm.nih.gov/pubmed/32273812
http://dx.doi.org/10.1016/j.jsps.2020.03.002
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author AlAsmari, Abdullah F.
Ali, Nemat
AlAsmari, Fawaz
AlAnazi, Wael A.
AlShammari, Musaad A.
Al-Harbi, Naif O.
Alhoshani, Ali
As Sobeai, Homood M.
AlSwayyed, Mohammed
AlAnazi, Mohammed M.
AlGhamdi, Nader S.
author_facet AlAsmari, Abdullah F.
Ali, Nemat
AlAsmari, Fawaz
AlAnazi, Wael A.
AlShammari, Musaad A.
Al-Harbi, Naif O.
Alhoshani, Ali
As Sobeai, Homood M.
AlSwayyed, Mohammed
AlAnazi, Mohammed M.
AlGhamdi, Nader S.
author_sort AlAsmari, Abdullah F.
collection PubMed
description Gefitinib is an effective treatment for patients with locally advanced non-small cell lung cancer. However, it is associated with cardiotoxicity that can limit its clinical use. Liraglutide, a glucagon-like peptide 1 receptor agonist, showed potent cardioprotective effects with the mechanism is yet to be elucidated. Therefore, this study aimed to determine the efficiency of liraglutide in protecting the heart from damage induced by gefitinib. Adult male Wistar rats were randomly divided into control group, liraglutide group (200 µg/kg by i.p. injection), gefitinib group (30 mg/kg orally) and liraglutide plus gefitinib group. After 28 days, blood and tissue samples were collected for histopathological, biochemical, gene and protein analysis. We demonstrated that gefitinib treatment (30 mg/kg) resulted in cardiac damage as evidenced by histopathological studies. Furthermore, serum Creatine kinase-MB (CK-MB), N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac Troponin-I (cTnI) were markedly elevated in gefitinib group. Pretreatment with liraglutide (200 µg/kg), however, restored the elevation in serum markers and diminished gefitinib-induced cardiac damage. Moreover, liraglutide improved the gene and protein levels of anti-oxidant (superoxide dismutase) and decreased the oxidative stress marker (NF-κB). Mechanistically, liraglutide offered protection through upregulation of the survival kinases (ERK1/2 and Akt) and downregulation of stress-activated kinases (JNK and P38). In this study, we provide evidence that liraglutide protects the heart from gefitinib-induced cardiac damage through its anti-oxidant property and through the activation of survival kinases.
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spelling pubmed-71326012020-04-09 Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways AlAsmari, Abdullah F. Ali, Nemat AlAsmari, Fawaz AlAnazi, Wael A. AlShammari, Musaad A. Al-Harbi, Naif O. Alhoshani, Ali As Sobeai, Homood M. AlSwayyed, Mohammed AlAnazi, Mohammed M. AlGhamdi, Nader S. Saudi Pharm J Article Gefitinib is an effective treatment for patients with locally advanced non-small cell lung cancer. However, it is associated with cardiotoxicity that can limit its clinical use. Liraglutide, a glucagon-like peptide 1 receptor agonist, showed potent cardioprotective effects with the mechanism is yet to be elucidated. Therefore, this study aimed to determine the efficiency of liraglutide in protecting the heart from damage induced by gefitinib. Adult male Wistar rats were randomly divided into control group, liraglutide group (200 µg/kg by i.p. injection), gefitinib group (30 mg/kg orally) and liraglutide plus gefitinib group. After 28 days, blood and tissue samples were collected for histopathological, biochemical, gene and protein analysis. We demonstrated that gefitinib treatment (30 mg/kg) resulted in cardiac damage as evidenced by histopathological studies. Furthermore, serum Creatine kinase-MB (CK-MB), N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac Troponin-I (cTnI) were markedly elevated in gefitinib group. Pretreatment with liraglutide (200 µg/kg), however, restored the elevation in serum markers and diminished gefitinib-induced cardiac damage. Moreover, liraglutide improved the gene and protein levels of anti-oxidant (superoxide dismutase) and decreased the oxidative stress marker (NF-κB). Mechanistically, liraglutide offered protection through upregulation of the survival kinases (ERK1/2 and Akt) and downregulation of stress-activated kinases (JNK and P38). In this study, we provide evidence that liraglutide protects the heart from gefitinib-induced cardiac damage through its anti-oxidant property and through the activation of survival kinases. Elsevier 2020-04 2020-03-19 /pmc/articles/PMC7132601/ /pubmed/32273812 http://dx.doi.org/10.1016/j.jsps.2020.03.002 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
AlAsmari, Abdullah F.
Ali, Nemat
AlAsmari, Fawaz
AlAnazi, Wael A.
AlShammari, Musaad A.
Al-Harbi, Naif O.
Alhoshani, Ali
As Sobeai, Homood M.
AlSwayyed, Mohammed
AlAnazi, Mohammed M.
AlGhamdi, Nader S.
Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways
title Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways
title_full Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways
title_fullStr Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways
title_full_unstemmed Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways
title_short Liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of MAPK/NF-κB signaling pathways
title_sort liraglutide attenuates gefitinib-induced cardiotoxicity and promotes cardioprotection through the regulation of mapk/nf-κb signaling pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132601/
https://www.ncbi.nlm.nih.gov/pubmed/32273812
http://dx.doi.org/10.1016/j.jsps.2020.03.002
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