A switch in mechanism of action prevents doxorubicin-mediated cardiac damage.
Anthracycline chemotherapy
Doxorubicin-DNA adduct
Doxorubicin-induced cardiotoxicity
Formaldehyde-releasing prodrug
Triple negative breast cancer
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
22
10
2020
revised:
03
01
2021
accepted:
05
01
2021
pubmed:
12
1
2021
medline:
2
7
2021
entrez:
11
1
2021
Statut:
ppublish
Résumé
Cancer patients treated with doxorubicin are at risk of congestive heart failure due to doxorubicin-mediated cardiotoxicity via topoisomerase IIβ poisoning. Acute cardiac muscle damage occurs in response to the very first dose of doxorubicin, however, cardioprotection has been reported after co-treatment of doxorubicin with acyloxyalkyl ester prodrugs. The aim of this study was to examine the role played by various forms of acute cardiac damage mediated by doxorubicin and determine a mechanism for the cardioprotective effect of formaldehyde-releasing prodrug AN-9 (pivaloyloxymethyl butyrate). Doxorubicin-induced cardiac damage in BALB/c mice bearing mammary tumours was established with a single dose of doxorubicin (4 or 16 mg/kg) administered alone or in combination with AN-9 (100 mg/kg). AN-9 protected the heart from doxorubicin-induced myocardial apoptosis and also significantly reduced dsDNA breaks, independent from the level of doxorubicin biodistribution to the heart. Covalent incorporation of [
Identifiants
pubmed: 33428897
pii: S0006-2952(21)00006-X
doi: 10.1016/j.bcp.2021.114410
pii:
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Cardiotonic Agents
0
Doxorubicin
80168379AG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114410Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.