Alteration of cardiac energetics and mitochondrial function in doxorubicin‑induced cardiotoxicity: Molecular mechanism and prospective implications (Review).

Abstract

Doxorubicin (DOX)‑induced cardiotoxicity (DIC) remains a critical challenge in cancer therapy, significantly limiting its use in clinical practice. The underlying mechanisms involve disruptions in cardiac metabolism and mitochondrial dysfunction. The heart relies on mitochondrial oxidative phosphorylation to produce ATP, which is essential for maintaining both contraction and relaxation. DOX disrupts glucose metabolism and fatty acid oxidation, resulting in energy shortages and excessive production of reactive oxygen species (ROS). These ROS contribute to mitochondrial damage, organelle malfunction and eventually cardiomyocyte death. This review describes the pathophysiological aspects of DIC, emphasising the molecular mechanisms underlying mitochondrial dysfunction and metabolic dysregulation in the heart during DIC progression. Additionally, the potential diagnostics, therapeutic interventions and drugs targeting metabolic pathways are summarised, focusing on metabolic modulation, combining non‑pharmacological therapies, such as exercise, fasting and mitochondrial transplantation, and approaches to enhance mitochondrial quality control, offering promising theoretical insights and practical strategies for DIC prevention and management.