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Involvement of ferritin heavy chain in the preventive effect of metformin against doxorubicin-induced cardiotoxicity

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dc.contributor.authorAsensio López, Maria del Carmen
dc.contributor.authorSánchez Mas, Jesús
dc.contributor.authorPascual Figal, Domingo A
dc.contributor.authorAbenza, Sergio
dc.contributor.authorPerez Martinez, Maria T
dc.contributor.authorValdés, Mariano
dc.contributor.authorLax Pérez, Antonio Manuel
dc.contributor.departmentMedicina
dc.date.accessioned2024-07-15T11:20:39Z
dc.date.available2024-07-15T11:20:39Z
dc.date.issued2013-04
dc.description© 2012 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.2012.09.009
dc.description.abstractDoxorubicin is a wide-spectrum chemotherapeutic agent, although a cumulative dose may cause cardiac damage and lead to heart failure. Doxorubicin cardiotoxicity is dependent on the intracellular iron pool and manifests itself by increasing oxidative stress. Our group has recently shown the ability of metformin, an oral antidiabetic with cardiovascular benefits, to protect cardiomyocytes from doxorubicin-induced damage. This work aimed to study whether metformin is able to modulate the expression of ferritin, the major intracellular iron storage protein, in cardiomyocytes and whether it is involved in their protection. The addition of metformin to adult mouse cardiomyocytes (HL-1 cell line) induced both gene and protein expression of the ferritin heavy chain (FHC) in a time-dependent manner. The silencing of FHC expression with siRNAs inhibited the ability of metformin to protect cardiomyocytes from doxorubicin-induced damage, in terms of the percentage of cell viability, the levels of reactive oxygen species, and the activity of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase). In addition, metformin induced the activation of NF-κB in HL-1 cells, whereas preincubation with SN50, an inhibitor of NF-κB, blocked the upregulation of the FHC and the protective effect mediated by metformin. Taken together, these results provide new knowledge on the protective actions of metformin against doxorubicin-induced cardiotoxicity by identifying FHC and NF-κB as the major mediators of this beneficial effect.es
dc.formatapplication/pdfes
dc.format.extent13es
dc.identifier.citationFree Radical Biology and Medicine. 2013, Vol. 57, pp. 188-200
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2012.09.009
dc.identifier.issnPrint: 0891-5849
dc.identifier.issnElectronic: 1873-4596
dc.identifier.urihttp://hdl.handle.net/10201/143090
dc.languageenges
dc.publisherElsevier
dc.relationThis study was supported in part by Grant 11857/PI/09 (to D.A.P.-F.) from Fundación Séneca, 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.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0891584912011343
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectDoxorubicines
dc.subjectMetformines
dc.subjectFerritines
dc.subjectOxidative stresses
dc.subjectCardiotoxicityes
dc.titleInvolvement of ferritin heavy chain in the preventive effect of metformin against doxorubicin-induced cardiotoxicityes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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