Iron replacement in anthracycline-related cardiac dysfunction: fuel on the fire?

Graphical Abstract Graphical Abstract Iron-mediated molecular mechanisms of anthracycline (simplified to DOX) induced cardiotoxicity: anthracyclines increase cardiac iron uptake by upregulating myocyte transferrin receptor expression and can liberate iron from iron–sulfur-containing proteins like ac...

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Bibliographic Details
Published in:European heart journal 2024-09, Vol.45 (34), p.3132-3134
Main Authors: Nazir, Muhummad Sohaib, Lyon, Alexander R, Southworth, Richard
Format: Article
Language:English
Subjects:
Anthracyclines - adverse effects
Cardiotoxicity - etiology
Humans
Iron - adverse effects
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Summary:Graphical Abstract Graphical Abstract Iron-mediated molecular mechanisms of anthracycline (simplified to DOX) induced cardiotoxicity: anthracyclines increase cardiac iron uptake by upregulating myocyte transferrin receptor expression and can liberate iron from iron–sulfur-containing proteins like aconitase and iron regulatory proteins (IRPs) to elevate the cytosolic labile iron pool (cLIP). This iron can complex with anthracyclines to redox cycle with cytosolic oxidases to drive reactive oxygen species (ROS) generation via Fenton and Haber–Weiss (H–W) reactions. This iron also accumulates in mitochondria, which cannot store it (because anthracyclines downregulate ferritin expression) and cannot remove it (because anthracyclines inhibit the mitochondrial iron exporter ABCB8). The resultant elevated mitochondrial labile iron pool (mLIP) forms complexes with anthracyclines that cycle at Complex I of the electron transport chain to drive ROS production, mitochondrial damage, and metabolic derangement. TCA, tricarboxylic acid. Figure courtesy of Dr Melissa Gargaro, King’s College London
ISSN:0195-668X
1522-9645
1522-9645
DOI:10.1093/eurheartj/ehae411