Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784686422775562240 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9005275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT guofuding cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT wangyueyi cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT wangjun cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT liuzhihao cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT laiyanqiu cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT zhouzhen cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT liuzihan cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT zhouyuyang cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT xuxiao cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT lizeyan cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT wangmeng cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT yufu cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT huruijie cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT zhouliping cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway AT jianghong cholineprotectstheheartfromdoxorubicininducedcardiotoxicitythroughvagalactivationandnrf2ho1pathway |