Yang Bai1, Qiang Chen2, Yun-Peng Sun1, Xuan Wang3, Li Lv4, Li-Ping Zhang5, Jin-Sha Liu6, Song Zhao7, Xiao-Lu Wang4. 1. The Cardiac Surgery Department, The First Hospital of Jilin University, Changchun, China. 2. School of Public Health, Jilin University, Changchun, China. 3. Department of Pharmacology, The College of Basic Medicine of Jilin University, Changchun, China. 4. The Jilin Province People's Hospital, Changchun, China. 5. The Cardiovascular Department, The First Hospital of Jilin University, Changchun, China. 6. The Cardiovascular Department, The China-Japan Union Hospital of Jilin University, Changchun, China. 7. The Spine Surgery Department, The First Hospital of Jilin University, Changchun, China.
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.
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.