Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy

Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, thre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Huan He, Liang Wang, Yang Qiao, Bin Yang, Dong Yin, Ming He
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	AMP-Activated protein kinase α2 Autophagy Cardiotoxicity Doxorubicin Epigallocatechin-3-gallate Ferroptosis Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8c83b72294f346a0b2e9f1e91941b404
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8c83b72294f346a0b2e9f1e91941b404
record_format	dspace
spelling	oai:doaj.org-article:8c83b72294f346a0b2e9f1e91941b4042021-11-12T04:33:12ZEpigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy2213-231710.1016/j.redox.2021.102185https://doaj.org/article/8c83b72294f346a0b2e9f1e91941b4042021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2213231721003451https://doaj.org/toc/2213-2317Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets. Here, we confirmed in vitro and in vivo that at least autophagy, apoptosis, and ferroptosis are involved in Dox cardiotoxicity-induced damage. When the neonatal rat cardiomyocytes and H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress and abnormal lipid metabolism, and thereby alleviate Dox cardiotoxicity-induced ferroptosis and protect the myocardium according to multiple functional, enzymatic, and morphological indices. The underlying mechanism was verified to involve the upregulation and activation of AMP-activated protein kinase α2, which promoted adaptive autophagy, increased energy supply, and maintained mitochondrial function. We believe that epigallocatechin-3-gallate is a candidate phytochemical against Dox-induced cardiotoxicity.Huan HeLiang WangYang QiaoBin YangDong YinMing HeElsevierarticleAMP-Activated protein kinase α2AutophagyCardiotoxicityDoxorubicinEpigallocatechin-3-gallateFerroptosisMedicine (General)R5-920Biology (General)QH301-705.5ENRedox Biology, Vol 48, Iss , Pp 102185- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AMP-Activated protein kinase α2 Autophagy Cardiotoxicity Doxorubicin Epigallocatechin-3-gallate Ferroptosis Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	AMP-Activated protein kinase α2 Autophagy Cardiotoxicity Doxorubicin Epigallocatechin-3-gallate Ferroptosis Medicine (General) R5-920 Biology (General) QH301-705.5 Huan He Liang Wang Yang Qiao Bin Yang Dong Yin Ming He Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy
description	Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets. Here, we confirmed in vitro and in vivo that at least autophagy, apoptosis, and ferroptosis are involved in Dox cardiotoxicity-induced damage. When the neonatal rat cardiomyocytes and H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress and abnormal lipid metabolism, and thereby alleviate Dox cardiotoxicity-induced ferroptosis and protect the myocardium according to multiple functional, enzymatic, and morphological indices. The underlying mechanism was verified to involve the upregulation and activation of AMP-activated protein kinase α2, which promoted adaptive autophagy, increased energy supply, and maintained mitochondrial function. We believe that epigallocatechin-3-gallate is a candidate phytochemical against Dox-induced cardiotoxicity.
format	article
author	Huan He Liang Wang Yang Qiao Bin Yang Dong Yin Ming He
author_facet	Huan He Liang Wang Yang Qiao Bin Yang Dong Yin Ming He
author_sort	Huan He
title	Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy
title_short	Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy
title_full	Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy
title_fullStr	Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy
title_full_unstemmed	Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy
title_sort	epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating ampkα2 and activating adaptive autophagy
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/8c83b72294f346a0b2e9f1e91941b404
work_keys_str_mv	AT huanhe epigallocatechin3gallatepretreatmentalleviatesdoxorubicininducedferroptosisandcardiotoxicitybyupregulatingampka2andactivatingadaptiveautophagy AT liangwang epigallocatechin3gallatepretreatmentalleviatesdoxorubicininducedferroptosisandcardiotoxicitybyupregulatingampka2andactivatingadaptiveautophagy AT yangqiao epigallocatechin3gallatepretreatmentalleviatesdoxorubicininducedferroptosisandcardiotoxicitybyupregulatingampka2andactivatingadaptiveautophagy AT binyang epigallocatechin3gallatepretreatmentalleviatesdoxorubicininducedferroptosisandcardiotoxicitybyupregulatingampka2andactivatingadaptiveautophagy AT dongyin epigallocatechin3gallatepretreatmentalleviatesdoxorubicininducedferroptosisandcardiotoxicitybyupregulatingampka2andactivatingadaptiveautophagy AT minghe epigallocatechin3gallatepretreatmentalleviatesdoxorubicininducedferroptosisandcardiotoxicitybyupregulatingampka2andactivatingadaptiveautophagy
_version_	1718431303137755136

Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy

Ejemplares similares