Yellow Wine Polyphenolic Compounds prevents Doxorubicin-induced cardiotoxicity through activation of the Nrf2 signalling pathway.
J Cell Mol Med
; 23(9): 6034-6047, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31225944
ABSTRACT
Doxorubicin (DOX) is considered as the major culprit in chemotherapy-induced cardiotoxicity. Yellow wine polyphenolic compounds (YWPC), which are full of polyphenols, have beneficial effects on cardiovascular disease. However, their role in DOX-induced cardiotoxicity is poorly understood. Due to their antioxidant property, we have been suggested that YWPC could prevent DOX-induced cardiotoxicity. In this study, we found that YWPC treatment (30 mg/kg/day) significantly improved DOX-induced cardiac hypertrophy and cardiac dysfunction. YWPC alleviated DOX-induced increase in oxidative stress levels, reduction in endogenous antioxidant enzyme activities and inflammatory response. Besides, administration of YWPC could prevent DOX-induced mitochondria-mediated cardiac apoptosis. Mechanistically, we found that YWPC attenuated DOX-induced reactive oxygen species (ROS) and down-regulation of transforming growth factor beta 1 (TGF-ß1)/smad3 pathway by promoting nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nucleus translocation in cultured H9C2 cardiomyocytes. Additionally, YWPC against DOX-induced TGF-ß1 up-regulation were abolished by Nrf2 knockdown. Further studies revealed that YWPC could inhibit DOX-induced cardiac fibrosis through inhibiting TGF-ß/smad3-mediated ECM synthesis. Collectively, our results revealed that YWPC might be effective in mitigating DOX-induced cardiotoxicity by Nrf2-dependent down-regulation of the TGF-ß/smad3 pathway.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
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Cardiomegalia
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Fator 2 Relacionado a NF-E2
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Polifenóis
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Antibióticos Antineoplásicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article