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Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway

Choline is a precursor of the major neurotransmitter acetylcholine and has been demonstrated beneficial in diverse models of cardiovascular disease. Here, we sought to verify that choline protects the heart from DOX-induced cardiotoxicity and the underlying mechanisms. The results showed that DOX tr...

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Autores principales: Guo, Fuding, Wang, Yueyi, Wang, Jun, Liu, Zhihao, Lai, Yanqiu, Zhou, Zhen, Liu, Zihan, Zhou, Yuyang, Xu, Xiao, Li, Zeyan, Wang, Meng, Yu, Fu, Hu, Ruijie, Zhou, Liping, Jiang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005275/
https://www.ncbi.nlm.nih.gov/pubmed/35422894
http://dx.doi.org/10.1155/2022/4740931
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author Guo, Fuding
Wang, Yueyi
Wang, Jun
Liu, Zhihao
Lai, Yanqiu
Zhou, Zhen
Liu, Zihan
Zhou, Yuyang
Xu, Xiao
Li, Zeyan
Wang, Meng
Yu, Fu
Hu, Ruijie
Zhou, Liping
Jiang, Hong
author_facet Guo, Fuding
Wang, Yueyi
Wang, Jun
Liu, Zhihao
Lai, Yanqiu
Zhou, Zhen
Liu, Zihan
Zhou, Yuyang
Xu, Xiao
Li, Zeyan
Wang, Meng
Yu, Fu
Hu, Ruijie
Zhou, Liping
Jiang, Hong
author_sort Guo, Fuding
collection PubMed
description Choline is a precursor of the major neurotransmitter acetylcholine and has been demonstrated beneficial in diverse models of cardiovascular disease. Here, we sought to verify that choline protects the heart from DOX-induced cardiotoxicity and the underlying mechanisms. The results showed that DOX treatment decreased left ventricular ejection fraction and fractional shortening and increased serum cardiac markers and myocardial fibrosis, which were alleviated by cotreatment with choline. DOX-induced cardiotoxicity was accompanied by increases in oxidative stress, inflammation, and apoptosis, which were rectified by choline cotreatment. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1), which are antioxidant markers, were lowered by DOX and upregulated by choline. Moreover, DOX significantly decreased serum acetylcholine levels and the high-frequency component of heart rate variability and increased serum norepinephrine levels and the low-frequency component; these effects were rescued by choline administration. Interestingly, the protective effects of choline could be partially reversed by administration of the muscarinic receptor antagonist atropine. This suggests that choline might be a promising adjunct therapeutic agent to alleviate DOX-induced cardiotoxicity.
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spelling pubmed-90052752022-04-13 Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway Guo, Fuding Wang, Yueyi Wang, Jun Liu, Zhihao Lai, Yanqiu Zhou, Zhen Liu, Zihan Zhou, Yuyang Xu, Xiao Li, Zeyan Wang, Meng Yu, Fu Hu, Ruijie Zhou, Liping Jiang, Hong Oxid Med Cell Longev Research Article Choline is a precursor of the major neurotransmitter acetylcholine and has been demonstrated beneficial in diverse models of cardiovascular disease. Here, we sought to verify that choline protects the heart from DOX-induced cardiotoxicity and the underlying mechanisms. The results showed that DOX treatment decreased left ventricular ejection fraction and fractional shortening and increased serum cardiac markers and myocardial fibrosis, which were alleviated by cotreatment with choline. DOX-induced cardiotoxicity was accompanied by increases in oxidative stress, inflammation, and apoptosis, which were rectified by choline cotreatment. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1), which are antioxidant markers, were lowered by DOX and upregulated by choline. Moreover, DOX significantly decreased serum acetylcholine levels and the high-frequency component of heart rate variability and increased serum norepinephrine levels and the low-frequency component; these effects were rescued by choline administration. Interestingly, the protective effects of choline could be partially reversed by administration of the muscarinic receptor antagonist atropine. This suggests that choline might be a promising adjunct therapeutic agent to alleviate DOX-induced cardiotoxicity. Hindawi 2022-04-05 /pmc/articles/PMC9005275/ /pubmed/35422894 http://dx.doi.org/10.1155/2022/4740931 Text en Copyright © 2022 Fuding Guo et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Guo, Fuding
Wang, Yueyi
Wang, Jun
Liu, Zhihao
Lai, Yanqiu
Zhou, Zhen
Liu, Zihan
Zhou, Yuyang
Xu, Xiao
Li, Zeyan
Wang, Meng
Yu, Fu
Hu, Ruijie
Zhou, Liping
Jiang, Hong
Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway
title Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway
title_full Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway
title_fullStr Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway
title_full_unstemmed Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway
title_short Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway
title_sort choline protects the heart from doxorubicin-induced cardiotoxicity through vagal activation and nrf2/ho-1 pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005275/
https://www.ncbi.nlm.nih.gov/pubmed/35422894
http://dx.doi.org/10.1155/2022/4740931
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