Header

UZH-Logo

Maintenance Infos

New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics


Tokarska-Schlattner, M; Zaugg, M; Zuppinger, C; Wallimann, T; Schlattner, U (2006). New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics. Journal of Molecular and Cellular Cardiology, 41(3):389-405.

Abstract

Cardiotoxic side-effects represent a serious complication of anticancer therapy with anthracyclines, in particular with doxorubicin (DXR) being the leading drug of the group. Different hypotheses, accentuating various mechanisms and/or targets, have been proposed to explain DXR-induced cardiotoxicity. This review focuses on the myocardial energetic network as a target of DXR toxic action in heart and highlights the recent advances in understanding its role in development of the DXR related cardiac dysfunction. We present a survey of DXR-induced defects in different steps of cardiac energy metabolism, including reduction of oxidative capacity of mitochondria, changes in the profile of energy substrate utilization, disturbance of energy transfer between sites of energy production and consumption, as well as defects in energy signaling. Considering the wide spectrum and diversity of the changes reported, we attempt to integrate these facts into a common framework and to discuss important functional and temporal relationships between DXR-induced events and the possible underlying molecular mechanisms.

Abstract

Cardiotoxic side-effects represent a serious complication of anticancer therapy with anthracyclines, in particular with doxorubicin (DXR) being the leading drug of the group. Different hypotheses, accentuating various mechanisms and/or targets, have been proposed to explain DXR-induced cardiotoxicity. This review focuses on the myocardial energetic network as a target of DXR toxic action in heart and highlights the recent advances in understanding its role in development of the DXR related cardiac dysfunction. We present a survey of DXR-induced defects in different steps of cardiac energy metabolism, including reduction of oxidative capacity of mitochondria, changes in the profile of energy substrate utilization, disturbance of energy transfer between sites of energy production and consumption, as well as defects in energy signaling. Considering the wide spectrum and diversity of the changes reported, we attempt to integrate these facts into a common framework and to discuss important functional and temporal relationships between DXR-induced events and the possible underlying molecular mechanisms.

Statistics

Citations

148 citations in Web of Science®
172 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

3 downloads since deposited on 18 Mar 2009
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Institute of Anesthesiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:September 2006
Deposited On:18 Mar 2009 19:49
Last Modified:05 Apr 2016 13:05
Publisher:Elsevier
ISSN:0022-2828
Publisher DOI:https://doi.org/10.1016/j.yjmcc.2006.06.009
PubMed ID:16879835

Download

Preview Icon on Download
Filetype: PDF - Registered users only
Size: 1MB
View at publisher