Key result
Anthracyclines induce cardiotoxicity by increasing cardiac iron uptake and elevating labile iron pools, driving reactive oxygen species generation and mitochondrial damage.
Anthracyclines disrupt cardiac iron homeostasis, leading to toxic iron accumulation and ROS generation, raising concerns about the safety of iron replacement in anthracycline-related cardiac dysfunction.
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
No takes yet. Share an insight, caveat, or question.
Nazir et al. (2024) conducted a review in Anthracycline-induced cardiotoxicity. Anthracyclines was evaluated. Anthracyclines induce cardiotoxicity by increasing cardiac iron uptake and elevating labile iron pools, driving reactive oxygen species generation and mitochondrial damage.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: