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

Abstract:

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.

journal_name

Cardiovasc Ther

authors

Bai Y,Chen Q,Sun YP,Wang X,Lv L,Zhang LP,Liu JS,Zhao S,Wang XL

doi

10.1111/1755-5922.12277

subject

Has Abstract

pub_date

2017-10-01 00:00:00

issue

5

eissn

1755-5914

issn

1755-5922

journal_volume

35

pub_type

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