Sulforaphane protection against the development of doxorubicin‐induced chronic heart failure is associated with Nrf2 Upregulation

Summary Background Doxorubicin (DOX) is an anthracycline antitumor drug. However, its clinical use is limited by dose‐dependent cardiotoxicity and even progresses to chronic heart failure (CHF). Objective This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX‐...

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Published in:Cardiovascular therapeutics 2017-10, Vol.35 (5), p.n/a
Main Authors: Bai, Yang, Chen, Qiang, Sun, Yun‐Peng, Wang, Xuan, Lv, Li, Zhang, Li‐Ping, Liu, Jin‐Sha, Zhao, Song, Wang, Xiao‐Lu
Format: Article
Language:English
Subjects:
Animals
Cardiotoxicity
Cell Line
Chronic Disease
Chronic heart failure
Collagen - metabolism
Disease Models, Animal
Doxorubicin
Fibrosis
Heart failure
Heart Failure - chemically induced
Heart Failure - metabolism
Heart Failure - physiopathology
Heart Failure - prevention & control
Isothiocyanates - pharmacology
Male
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
Oxidative stress
Oxidative Stress - drug effects
Protective Agents - pharmacology
Rats, Sprague-Dawley
Rodents
Signal Transduction - drug effects
Sulforaphane
Time Factors
Transcription, Genetic - drug effects
Up-Regulation
Ventricular Function, Left - drug effects
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Summary:Summary Background Doxorubicin (DOX) is an anthracycline antitumor drug. However, its clinical use is limited by dose‐dependent cardiotoxicity and even progresses to chronic heart failure (CHF). Objective This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX‐induced CHF. Methods Male Sprague‐Dawley rats which received treatment for 6 weeks were divided into four groups (n=30 per group): control, SFN, DOX and DOX plus SFN group. Results Results revealed that DOX induced progressive cardiac damage as indicated by increased cardiac injury markers, cardiac inflammation, fibrosis and oxidative stress. SFN significantly prevented DOX‐induced progressive cardiac dysfunction between 2‐6 weeks and prevented DOX‐induced cardiac function deterioration. Furthermore, it significantly decreased ejection fraction and increased the expression of brain natriuretic peptide. SFN also almost completely prevented DOX‐induced cardiac oxidative stress, inflammation and fibrosis. SFN upregulated NF‐E2‐related factor 2 (Nrf2) expression and transcription activity, which was reflected by the increased mRNA expression of Nrf2 and its downstream genes. Furthermore, in cultured H9c2 cardiomyocytes, the protective effect of SFN against DOX‐induced fibrotic and inflammatory responses was abolished by Nrf2 silencing. Conclusion We arrived at the conclusion that DOX‐induced CHF can be prevented by SFN through the upregulation of Nrf2 expression and transcriptional function.
ISSN:1755-5914
1755-5922
DOI:10.1111/1755-5922.12277