Artículo
Short-term doxorubicin cardiotoxic effects: involvement of cardiac Thyrotropin Releasing Hormone system
Peres Diaz, Ludmila Soledad
; Schuman, Mariano Luis
; Aisicovich, Maia
; Toblli, Jorge Eduardo
; Pirola, Carlos José
; Landa, Maria Silvina
; Garcia, Silvia Ines
Fecha de publicación:
08/2020
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Life Sciences
ISSN:
0024-3205
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Doxorubicin is an antineoplastic in the anthracycline class widely used for the treatment of several solid tumors and blood cancers. Cardiotoxicity is the major dose-limiting adverse effect of the drug. Chronic and accumulated doxorubicin administration cause myocyte damage and myocardial fibrosis. Doxorubicin-associated cardiotoxicity can be also observed after a short-course drug treatment even without clinical evidence of cardiac disease. Nevertheless, acute underlying mechanisms involved in the initiation of drug-induced cardiotoxicity remain poorly explored despite their similarities with pathophysiological conditions where cardiac TRH (cTRH) plays a central role. We showed that cTRH mediates myocardial injury induced by hypertension, and angiotensin II. Further, cTRH overexpression induces cardiac apoptosis, hypertrophy and fibrosis. Aim: To demonstrate that cTRH could mediate acute doxorubicin cardiotoxicity. Main method: A single injection of doxorubicin (10 mg kg/day i.p.) was used to evaluate acute cardiac damage in a short-term experimental model of doxorubicin-induced cardiotoxicity. While inhibiting cTRH by small interfering RNA (siRNA), we evaluated the progression of cardiotoxicity. Key findings: We found a doxorubicin-induced TRH overexpression in the LV, which was associated with apoptosis, hypertrophy and fibrosis. siRNA-mediated cTRH suppression prevented the doxorubicin-associated cardiac histological lesions. Significances: doxorubicin requires an active cardiac TRH system to promote heart injury.
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Articulos(IDIM)
Articulos de INST.DE INVEST.MEDICAS
Articulos de INST.DE INVEST.MEDICAS
Citación
Peres Diaz, Ludmila Soledad; Schuman, Mariano Luis; Aisicovich, Maia; Toblli, Jorge Eduardo; Pirola, Carlos José; et al.; Short-term doxorubicin cardiotoxic effects: involvement of cardiac Thyrotropin Releasing Hormone system; Pergamon-Elsevier Science Ltd; Life Sciences; 261; 8-2020; 1-7
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