Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system

Asensio López, María del Carmen; Lax Pérez, Antonio Manuel; Pascual Figal, Domingo A; Valdés, Mariano; Sánchez Mas, Jesús

Publication:
Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system

dc.contributor.author	Asensio López, María del Carmen
dc.contributor.author	Lax Pérez, Antonio Manuel
dc.contributor.author	Pascual Figal, Domingo A
dc.contributor.author	Valdés, Mariano
dc.contributor.author	Sánchez Mas, Jesús
dc.contributor.department	Medicina
dc.date.accessioned	2024-07-15T11:32:07Z
dc.date.available	2024-07-15T11:32:07Z
dc.date.issued	2011-11-15
dc.description	© 2011 Elsevier Inc. This document is the Published version of a Published Work that appeared in final form in Free Radical Biology and Medicine. To access the final edited and published work see https://doi.org/10.1016/j.freeradbiomed.2011.08.015
dc.description.abstract	Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. Metformin exerts cardioprotective actions via AMP-activated protein kinase (AMPK) and increases the expression of adiponectin and its receptors (adipoR1 and adipoR2) in skeletal muscle and adipose tissue, but its effect on cardiac tissue is still unknown. This work aimed to study whether metformin exerts any protective action against the cardiotoxicity of doxorubicin and whether the cardiac system of adiponectin is involved in any such action. The addition of doxorubicin (5μM) to adult mouse cardiomyocytes (HL-1 cell line) induced apoptosis, which was characterized by a loss of cell viability, activation of caspases, and fragmentation of the genetic material. Doxorubicin treatment also caused a decrease in the activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase. Pretreatment with metformin (4mM, 24h) provided protection against doxorubicin-induced damage. This pretreatment significantly increased cell viability, attenuated the activation of caspases and the fragmentation of genetic material, and restored the antioxidant activity. In addition, metformin up-regulated the expression of adiponectin and its receptors, adipoR1 and adipoR2, in cardiomyocytes. In contrast, silencing either adipoR1 or adipoR2 with siRNA inhibited the AMPK activation and the protective effects of metformin. Taken together, these results demonstrate that metformin protects cardiomyocytes from doxorubicin-induced damage and that the cardiac adiponectin system plays an important role in this protective action.	es
dc.embargo.terms	SI
dc.format	application/pdf	es
dc.format.extent	11	es
dc.identifier.doi	https://doi.org/10.1016/j.freeradbiomed.2011.08.015
dc.identifier.eisbn	Free Radical Biology and Medicine, 2011, Vol. 51, Issue 10, pp. 1861-1871	es
dc.identifier.issn	Print: 0891-5849
dc.identifier.issn	Electronic: 1873-4596
dc.identifier.uri	http://hdl.handle.net/10201/143114
dc.language	eng	es
dc.publisher	Elsevier
dc.relation	This study was supported in part by Grant-CajaMurcia (to J.S.-M.) from the Fundación para la Formación e Investigación Sanitarias, Murcia, Spain; by Grant PS09/02106 (to M.V.) from the Ministerio de Sanidad, Madrid, Spain; and by the national network of investigation in heart failure “REDINSCOR” RD06/0003/0013.	es
dc.relation.publisherversion	https://www.sciencedirect.com/science/article/pii/S0891584911005259?via%3Dihub#aep-abstract-id15
dc.rights	info:eu-repo/semantics/embargoedAccess	es
dc.subject	Doxorubicin	es
dc.subject	Metformin	es
dc.subject	Adiponectin	es
dc.subject	Cardiotoxicity	es
dc.subject	Oxidative stress	es
dc.subject	Apoptosis	es
dc.subject	Free radicals	es
dc.title	Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es